Clinical trial NCT02222922
Conditions: Neoplasms
Keywords: ADC PF-06647020 solid tumors tumors neoplasm metastasis TNBC triple negative breast cancer NSCLC non small cell lung cancer advanced metastatic breast cancer ovarian cancer OVCA
Sponsor: Pfizer
Start date: 2014-10-17; Completion date: 2019-11-05
Enrollment: 138 participants; Allocation: NON_RANDOMIZED; Intervention model: 

Brief summary:
To assess the safety and tolerability at increasing dose levels of PF-06647020 in patients with advanced solid tumors in order to determine the maximum tolerated dose and select the recommended Phase 2 dose.

Detailed description:

Arms: arm 1: Investigational drug infused over 60 minutes once every 21 days. arm 2: PF-06647020 combined with fluconazole arm 3: Investigational drug infused over 60 minutes once every 14 days (28 day cycle) arm 4: PF-06647020 combined with Avelumab administered by infusion
Interventions: intervention 1: PF-06647020 Q3W intervention 2: fluconazole intervention 3: PF-06647020 Q2W intervention 4: PF-06647020 combined with Avelumab
Intervention descriptions: intervention 1: Part 1: PF-06647020 will be administered intravenously every 21 days in cohorts of 2-4 patients starting at a dose of 0.20mg/kg. Increases in dose will continue until MTD is determined.

Part 2: Patients with triple negative breast cancer (pre-selected for PTK7 moderately high to high expression), non small cell lung cancer (pre-selected with moderate to high PTK7 expression) and ovarian cancer patients (unselected for PTK7 expression) will be treated at the MTD or Recommended Phase 2 Dose selected in Part 1. intervention 2: combination drug used for drug-drug interaction sub-study intervention 3: Part 1: PF-06647020 will be administered intravenously every 14 days in cohorts of 2-4 patients starting at a dose of 2.1 mg/kg. Increases in dose will continue until MTD is determined.

Part 2: Patients with non-small cell lung cancer (pre-selected for PTK7 moderate to high expression and ovarian cancer patients (unselected for PTK7 expression) will be treated at the MTD or Recommended Phase 2 Dose selected in Part 1. intervention 4: Part 2: Patients with ovarian cancer (unselected for PTK7 expression) will be treated with PF-0664702 plus Avelumab.

Protocol documents:
Prot_000.pdf: 
PF-06647020
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Final Protocol Amendment 8, 09 November 2017
Page 1
A FIRST-IN-HUMAN PHASE 1, DOSE ESCALATION, SAFETY AND 
PHARMACOKINETIC STUDY OF PF-06647020 IN ADULT PATIENTS WITH 
ADVANCED SOLID TUMORS
Compound:
PF-06647020
Compound Name:
Not applicable (N/A)
United States (US) Investigational New 
Drug (IND) Number:
European Clinical Trials Database 
(EudraCT) Number:
2014-003296-36
Protocol Number:
B7661001
Phase:
1
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Document History
Document
Version Date
Summary of Changes and Rationale
Amendment 8 
(United Kingdom 
only)
09 November 2017
The following changes are only for sites in the 
UK:
Section 4.3 Lifestyle Guidelines: Clarification 
added that a condom with or without 
spermicide is not considered a highly effective 
method of contraception in the UK.
Section 4.3 & Appendix 8, Section A6.2 
Exclusion Criteria: Additional criteria added to 
clarify that male patients must use 
contraception methods for an additional 
90 days (120 days for single agent, 150 days 
for combination) and that female partners of 
male patients must use a highly effective 
method of contraception.
Amendment 7
15 May 2017
Study Design Section and Section 3.1 Study 
Overview: Addition of Q2W regimen 
expansion sub-study, avelumab 
background/rationale for the Q2W 
combination cohort, and removal the Japanese 
PK/Safety sub-study (including revision to 
objectives/endpoints).  Increased number of 
patients (~190) and sites (~15-20). 
Schedule of Activities for Q3W Regimen: 
Modified Day 8 assessments for patients 
beginning at Cycle 8.
Section 1.2.4 Clinical Safety (PF-06647020): 
Updated clinical safety, PK and efficacy data.
Sections 1.9 Rationale for Japanese Sub-Study: 
This section was deleted and sub-study no 
longer planned, no patients were enrolled 
under this sub-study.
Section 9.1 Analysis Sets: Addition of 
immunogenicity and 
 
Section 9.5.1 Analysis of Pharmacokinetics: 
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Version Date
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Clarification was made to specific PK 
parameter to be calculated; Vss was added to 
replace Vd.
Reference Section: Included new references.
Appendix 8 Replace Japanese Sub study with 
Q2W Regimen Expansion Sub-Study: Details 
provided for Q2W regimen expansion, 
including a Schedule of Activities tables.
All other changes are minor in nature added to 
this amendment to provide clarity and 
additional information.
Amendment 6
26 September 2016
Study Design: Addition of Japan sub-study to 
evaluate safety and pharmacokinetics (PK) in 
approximately 12 patients.
Study Design: Increased number of sites 
participating in Part 2 (8-12 sites).
Study Objectives and Endpoints for Part 2: 
Addition of primary and secondary 
objectives/endpoints as a result of inclusion of 
the Japanese sub-study. 
 
 
Section 1.9 Rationale for Japanese Sub-Study 
and Section 1.9.1 Starting dose in Japanese 
Patients: Included to provide rationale and 
information on doses that will be evaluated.
Section 4.1 Inclusion Criteria 2.c.2 and 2.c.3: 
Added liposomal doxorubicin as approved 
agent for second and third prior line of therapy.
Section 7.5.2 Immunophenotyping: Clarified 
that Japanese patients will not have 
immunophenotyping collection/analysis.
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Section 9.5.1 Analysis of Pharmacokinetics 
and Section 9.6 Safety Analysis: Clarified that 
there will be separate summaries of PK and 
safety parameters for DDI and Japanese 
patients.
Appendix 8. Japanese Sub-Study: Details 
provided for Japanese sub-study, including a 
Schedule of Activities table.
Amendment 5
06 July 2016
Study Design, Section 3.5 Dose Expansion 
Phase (Part 2), Section 9.3 Sample Size 
Determination: Additional enrollment of 
25 OVCA patients in Part 2 included.
Section 1.7 Clinical Experience: Updated 
clinical experience data included.
Section 5.7.4 Anti Diarrhea, Anti Emetic 
Therapy: Updated to allow for prophylaxis 
prior to Cycle 1 and subsequent cycles. 
Section 7.1.3 Laboratory Safety Assessments: 
Updated to align with current Protocol 
Template.
 
 
 
Section 7.7 Immunogenicity Evaluations: 
Revised to be consistent with language in 
Schedule of Activities footnote. 
Section 7.8.2 Additional Research: Updated to 
align with current Protocol Template.
Section 10 Quality Control and Quality 
Assurance, Section 11 Data Handling and 
Record Keeping, Section 12 Ethics, Section 
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Version Date
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14 Sponsor Discontinuation Criteria, Section 
15 Publication of Study Results: Updated to 
align with current Protocol Template.
Amendment 4
20 January 2016
Study Design, Objectives and Endpoints: 
Included new requirement for pre-selection of 
TNBC Part 2 patients.  Clarified that all 
analytes are being analyzed for the DDI sub 
study.
Section 1.5 PTK7 IHC Assay for 
PTK7 Expression,
 
 
Section 1.7 Clinical Experience: Updated 
clinical experience data included.
 
 
 
 
 
Section 7.2.1 Blood for PK analysis of ADC, 
Total Antibody, and Unconjugated Payload: 
Clarified protocol allowed windows for PK 
sampling.
Appendix 7 Drug-Drug Interaction Sub-Study 
and respective Schedule of Activity tables: 
Clarified that the 1st dose fluconazole will be 
administered on C1D21.  Clarified that 
Cycles 1 and 4 will have the same PK 
sampling requirements. 
Amendment 3
03 December 2015
Background and Rationale: Included ovarian 
cancer (OVCA) background information.
Study Design, Objectives, and Endpoints: 
Included 20 OVCA patients and a drug-drug 
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interaction (DDI) sub-study.
Schedule of Activities: Modified Day 
8 assessments for patients beginning at 
Cycle 13.  Addition of CA-125 serum 
biomarker for OVCA patients.
Section 1.7 Clinical Experience: Updated 
clinical experience data included.
Section 1.8 Rationale for Drug-Drug 
Interaction: Rationale provided.
Section 4.1 Inclusion Criteria: Additional 
criteria added for OVCA patients.
Appendix 7 Drug-Drug Interaction Sub-Study: 
Details provided for DDI study, including a 
Schedule of Activities table.
Amendment 2
05 August 2015
Background and Rationale: Provided Pfizer 
internal data that PTK7 expression is observed 
in ~84% of TNBC and NSCLC patients 
selected by PTK7 expression may be more 
likely to benefit.
Study Design: Part 2 patients will be enrolled 
at the recommended Phase 2 dose, as selected 
by the Sponsor and Investigators.  
 
 
Study Design: Increased number of sites 
participating in Part 2 (8-10 sites).
Schedule of Activities: Removed requirement 
that treatment must begin within 3 days of 
registration.
  
 
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Version Date
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Section 1.5 PTK7 Immunohistochemistry 
(IHC) Assay for PTK7 Expression: Added 
detail regarding assay to be utilized for Part 2.
Section 1.6 Triple Negative Breast Cancer and
NSCLC in Dose Expansion: Provided rationale 
for selecting TNBC and NSCLC indications.
Section 1.7 Clinical Experience: Provided 
ongoing study information for dose escalation 
portion.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Section 4.2 Exclusion Criteria: Revised 
Exclusion 2 to exclude anti-cancer therapy 
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within 3 weeks or 5 half-lives.
Section 4.3 Lifestyle Guidelines: Updated to 
align with updated Protocol Template.
Section 5.4.2 Dose Interruptions/Delays: 
Revised to allow patients more than 2 week 
delay if discussed and agreed with Sponsor.
Section 5.7.4 Anti Diarrhea, Anti Emetic 
Therapy: Revised to clarify that prophylaxis is 
permitted in subsequent cycles.
Section 6.4 Patient Withdrawal: Included 
section covering withdrawal due to disease 
progression, allowing patients to continue on 
study due to potential delayed response 
phenomena.
Section 7.1.5 12-lead ECG: Clarified 
measurements to be recorded from ECG.
 
 
 
 
 
 
Section 8 Adverse Event Reporting updated to 
align with updated Protocol Template.
Section 15 Publication of Study Results: 
Updated to align with updated Protocol 
Template.
Amendment 1
22 Sep 2014
Schedule of Activities: Remove language 
regarding repeat C1D1 coagulation and 
urinalysis samples.  Rationale: it is not 
applicable for this study.
 
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Section 3.2 Dose Escalation Phase Table 2: 
Inclusion of definition for U: unacceptable 
toxicity.  Rationale: previously omitted.
Section 3.3 DLT Definition: Include ALT or 
AST ≥3.0 x ULN concurrent with elevation in 
bilirubin ≥2.0 x ULN as a DLT.  Rationale: 
requested by the FDA. 
Section 3.4 MTD Definition and 9.2 Statistical 
Method for Estimating the MTD: Revise the 
definition of the MTD to be the highest dose 
with a DLT <33%.  Rationale: requested by 
the FDA.
Section 4.1 Inclusion Criteria: Revision to the 
inclusion criteria for NSCLC patients.  
Rationale: Requested by the FDA. 
Section 4.2 Exclusion Criteria: Add language 
to provide clarity.  Rationale: to make criteria 
more clear.
Section 4.2 Exclusion Criteria and 
5.7 Concomitant Treatment(s): Exclude the use 
of strong CYP3A inhibitors or inducers for 
patients enrolled in Part 1.  Rationale: 
Requested by the FDA
Section 5.4 Administration: Inclusion of 
language regarding treatment measures for 
infusion reactions and reference to 
Appendix 5.  Rationale: requested by the FDA. 
Section 5.4.3 Dose Reductions: Add to 
Table 4: ALT or AST ≥3.0 x ULN concurrent 
with elevation in bilirubin ≥2.0 x ULN as 
treatment termination.  Rationale: Requested 
by the FDA.
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Section 7.1.3 Laboratory Safety Assessments: 
Add it is acceptable for absolute or % values 
for lymphocytes, monocytes, eosinophils and 
basophils.  Rationale: provide flexibility to 
sites. 
and 
7.6 Immunogenicity Evaluations: Revise the 
amount of serum collected from whole blood 
samples.  Rationale: incorrect conversion 
provided. 
Original protocol
18 Jul 2014
Not Applicable (N/A)
This amendment incorporates all revisions to date, including amendments made at the 
request of country health authorities, institutional review boards/ethics committees 
(IRBs/ECs), etc. 
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PROTOCOL SUMMARY
Background and Rationale:
Antibody-drug conjugates (ADCs) were developed to improve the therapeutic indices of 
cytotoxic anti-cancer agents.  The strategy makes use of an immunoconjugate in which a 
cytotoxic agent is chemically or enzymatically linked to an antibody that selectively binds to 
an internalizing tumor-associated antigen. This strategy allows specific delivery of the 
cytotoxic agent to the tumor site while minimizing the exposure to normal tissues.
PF-06647020 is an anti-PTK7 ADC intended to be for the treatment of patients with cancer.  
PF-06647020 is comprised of a humanized anti-PTK7 monoclonal antibody (mAb) linked to 
an auristatin (Aur0101) via a cleavable cysteine-reactive linker. Auristatins are fully 
synthetic dolastatin-based pentapeptide inhibitor of tubulin polymerization that induce 
G2/M cell cycle arrest and cell death at low picomolar intracellular concentrations.13,14
PTK7 is a phylogenetically conserved member of the pseudokinase family of receptor 
tyrosine kinases (RTKs) with no observable kinase activity.4  Genetic and biochemical 
studies in multiple organisms have demonstrated a key function for PTK7 in planar cell 
polarity via the Wnt-pathway signaling, and PTK7-deficient embryos have developmental 
defects.3,7,11  In addition, PTK7 promotes cell survival in colorectal cancer and acute myeloid 
leukemia (AML), and PTK7 may promote resistance to chemotherapy in AML.9,12  
Bioinformatics and literature analysis have revealed that PTK7 mRNA expression levels in 
many types of tumors are higher than corresponding normal tissues including bladder, brain, 
breast, colorectal, gastric, kidney, liver, lung, pancreatic and skin cancer.  In addition, 
PTK7 was found to be enriched in cancer stem cells (CSCs), also known as tumor-initiating 
cells, harvested from patient-derived xenografted tumor models of triple negative breast 
cancer (TNBC) and non-small cell lung cancer (NSCLC) in preclinical studies.19  It was also 
reported that higher expression of PTK7 is linked to poor prognosis in patients with NSCLC
and TNBC who received chemotherapy, particularly in a subgroup patient population who 
received anthracycline treatment.2,19  In preclinical studies, PF-06647020 induced sustained 
tumor regressions in models of ovarian cancer (OVCA), NSCLC and TNBC.19
TNBC accounts for 15% to 20% of breast cancers and is diagnosed based on lack of estrogen 
receptor (ER) and progesterone receptor (PgR) expression by immunohistochemistry (IHC) 
and lack of HER2 over expression or gene amplification by IHC or in situ hybridization, 
respectively.  TNBC is a heterogeneous disease, not only on the molecular level, but also on 
the pathologic and clinical levels.  The majority of patients with TNBC respond with high 
sensitivity to chemotherapies including anthracyclines and taxanes in the neoadjuvant or 
adjuvant settings.  However, TNBC is associated with a significantly higher probability of 
relapse and poor overall survival (OS) in the first few years after diagnosis compared with 
other breast cancer subtypes. Positive expression of PTK7 in TNBC was observed in 
~84% of archived samples surveyed using a research grade IHC assay (Pfizer internal data).


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NSCLC accounts for approximately 85% cases of lung cancer, the leading cause of 
cancer-related mortality in the United States (US) and worldwide.  Most patients with 
NSCLC have locally advanced and distant metastatic disease (stage III/IV) at the time of 
presentation, which is associated with a poor prognosis with 5-year OS rate less than 10%.  
Although targeted therapies (eg, Erlotinib and Crizotinib) for patients with NSCLC whose 
tumors carry epidermal growth factor receptor (EGFR) mutation or are anaplastic lymphoma 
kinase (ALK)-positive have provided encouraging clinical outcome and promising 
immunotherapies are being developed, the unsatisfactory treatment outcomes in advanced 
NSCLC highlights the need of novel alternative therapies. In addition, PTK7 expression in 
NSCLC was observed to cover a dynamic range (Pfizer internal data), suggesting that patient 
selection by PTK7 expression levels may identify patients that may be more likely to benefit.
OVCA is the 6th most common malignancy in developed countries with approximately 
100,000 new cases resulting in nearly 65,000 deaths per year.15  Patients are typically treated 
with surgery followed by chemotherapy.  Initial therapy consists of combinations with 
platinum-containing agents which results in responses in 70-80% of patients.  However, the 
disease relapses in almost all patients requiring further therapy.  The timing of the relapse 
from the end of the platinum-containing regimen has been shown to be prognostic with 
platinum-resistant tumors (defined as progression while receiving initial therapy or relapse 
<6 months from end of initial regimen), as having the worst outcomes.16  Pegylated 
doxorubicin and topotecan are both indicated as single agents in patients with refractory 
OVCA.  In patients with platinum-resistant disease, both of these compounds result in 
response rate (RR) of 10-15%, progression free survival (PFS) of 14 weeks, and OS 
35-40 weeks highlighting the need for alternative therapies.16
Avelumab (MSB0010718C), a fully human antibody of the immunoglobulin G1 (IgG1) 
isotype, specifically targets and blocks programmed death-ligand 1 (PD-L1), the ligand for 
programmed death 1 (PD-1) receptor.  This interaction inhibits the suppressive effects of 
PD-L1 on cluster of differentiation 8 (CD8) positive T cells, and thus restores the cytotoxic 
T cell response against the tumor.  In preclinical studies, combination of avelumab with 
chemotherapies showed improved anti-tumor activity.20 Broad expression of PD-L1 was 
observed in ovarian cancer samples, and higher expression of PD-L1 was associated with 
significantly worse prognosis.32 Preliminary data from the ongoing OVCA Study EMR 
100070-001, which is being conducted by Merck KGaA/EMD Serono (EudraCT number 
2013-002834-19, NCT01772004) showed an overall response rate (ORR) of 10.7% (8/75) 
and stable disease (SD) in an additional 44% (33/75) of patients with advanced OVCA.  
Available adverse event (AE) and laboratory abnormality data from patients with advanced 
solid tumors treated with single-agent avelumab suggest an acceptable safety profile of the 
compound.  Most of the observed events were either in line with those expected in patients 
with advanced solid tumors or with similar class effects of monoclonal antibodies blocking 
the PD-1/PD-L1 axis.  Infusion-related reactions including hypersensitivity and immune 
related Adverse Events (irAEs)/autoimmune disorders have been identified as important risks 
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Several lines of evidence suggest that combining the PTK7-targeted ADC with avelumab 
would improve clinical outcomes.  In preclinical studies, combination of avelumab with 
chemotherapies showed improved anti-tumor activity.20  A recent preclinical study 
demonstrated that immunotherapy can be enhanced by localized chemotherapy but not 
systemic chemotherapy;21 indeed the PTK7-targeted ADC delivers a potent chemotherapy 
preferentially to the tumor cells and thus is distinguished from standard chemotherapies.  In 
addition, the PTK7-targeted ADC could stimulate anti-tumor immunity (and thus stimulate 
the response to avelumab) by multiple mechanisms: (1) auristatins can activate dendritic cells 
(Pfizer, unpublished data), and the expression of PTK7 on dendritic cells could increase the 
delivery of auristatin to those cells; (2) anti-angiogenic activity can promote immune cell 
infiltration into tumors, and the PTK7-targeted ADC specifically inhibits angiogenesis; 
(3) immunogenic cell death can stimulate anti-tumor immunity, and auristatins induce this 
phenotype in cancer cell lines.19
This is a first in human Phase 1, safety, pharmacokinetic (PK), and efficacy study of 
PF-06647020 in adult patients with advanced solid tumors, initially containing two parts:
dose escalation (Part 1) in patients with advanced solid tumors, followed by dose expansion 
(Part 2) in OVCA, TNBC, and NSCLC patients on a dosing schedule of every 3 weeks 
(Q3W).  The study has been expanded (Amendment 7) for safety, PK, and efficacy 
evaluation on a dosing schedule of every 2 weeks (Q2W) as a single agent treatment of 
PF-06647020 in OVCA and NSCLC, as well as combination treatment of PF-06647020 with 
avelumab in OVCA patients.
The design and procedure details of the Q2W regimen expansion unique from the main study 
can be found in Appendix 8.
Study Objectives and Endpoints (Original Protocol through Amendment 6)
Dose Escalation (Part 1) Objectives 
Primary Objectives

To assess safety and tolerability at increasing dose levels of PF-06647020
administered intravenously on an every 21-day dosing schedule to patients with 
advanced solid tumors unresponsive to currently available therapies, or for whom no 
standard therapy is available.

To determine the Maximum Tolerated Dose (MTD) and select the Recommended 
Phase 2 Dose (RP2D). 
Secondary Objectives 

To evaluate the overall safety profile.

To characterize the single and multiple dose PK of ADC (PF-06647020), total 
antibody (hu6M024 mAb) and unconjugated payload (PF-06380101).


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•
To evaluate the immunogenicity as measured by presence of anti-drug antibodies 
(ADA) in patients treated with PF-06647020.
•
To document any preliminary evidence of anti-tumor activity.
 
Dose Expansion (Part 2) Objectives
Primary Objective 
•
To further evaluate safety and tolerability of PF-06647020 at the MTD and to 
establish RP2D in patients with NSCLC, TNBC and OVCA.
Secondary Objectives
•
To evaluate the overall safety profile at the RP2D.
•
To evaluate preliminary anti-tumor activity of PF-06647020 at the RP2D in patients 
with NSCLC, TNBC and OVCA.
•
To characterize the single and multiple dose PK of ADC (PF-06647020), total 
antibody (hu6M024 mAb) and unconjugated payload (PF-06380101).
•
To evaluate the immunogenicity as measured by presence of ADA in patients treated 
with PF-06647020.
•
To evaluate the effect of the co-administration of fluconazole on the PK of 
unconjugated payload (PF-06380101), ADC (PF-00647020) and total antibody 
(hu6M024 mAb) following administration of ADC (PF-06647020).
•
To assess the effects of fluconazole on the safety and tolerability of a single dose of 
PF-06647020.
 
 
 
 
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Primary Endpoints
Primary Endpoints (Part 1)
•
First cycle Dose Limiting Toxicities (DLTs) in order to determine the MTD and 
RP2D of PF-06647020 administered by intravenous (IV) infusion in a 21-day dosing 
cycle.
Secondary Endpoints (Part 1)
•
Adverse events as characterized by type, frequency, severity [as graded by National 
Cancer Institute’s Common Terminology Criteria for Adverse Events 
(NCI CTCAE v.4.03)], timing, seriousness and relationship to study treatment.
•
Laboratory abnormalities as characterized by type, frequency, severity 
(as graded by NCI CTCAE v. 4.03) and timing.
•
Single and multi-dose PK parameters of multiple analytes [ADC (PF-06647020), total 
antibody (hu6M024 mAb) and unconjugated payload (PF-06380101)].
•
Incidence of anti-PF-066407020 antibodies. 
•
Preliminary evidence of anti-tumor activity based on RR, as assessed using the 
Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1. 
  
Primary Endpoints (Part 2)
•
Adverse events as characterized by type, frequency, severity (as graded by NCI 
CTCAE v.4.03), timing, seriousness and relationship to study treatment.
•
Laboratory abnormalities as characterized by type, frequency, severity 
(as graded by NCI CTCAE v. 4.03) and timing.
Secondary Endpoints (Part 2)
•
Objective response (OR), Duration of Response (DoR), Disease Control (DCR), Time 
to Progression (TTP), and PFS, as determined by Investigator [as assessed by 
RECIST version 1.1].
•
Single and multi-dose PK parameters of multiple analytes (ADC (PF-06647020), total 
antibody (hu6M024 mAb) and unconjugated payload (PF-06380101).
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•
Incidence of anti-PF-066407020 antibodies. 
•
The PK parameters of multiple analytes [ADC (PF-06647020), total antibody 
(hu6M024 mAb) and unconjugated payload (PF-06380101)] following ADC 
(PF-06647020) administration alone and when co-administered with fluconazole.
 
 
Objectives and Endpoints for Q2W Regimen Expansion
Primary Objectives
•
Part 1: To assess safety and tolerability at increasing dose levels of PF-06647020
administered intravenously as a single agent on a Q2W dosing schedule.
•
Part 1: To determine the MTD and select the RP2D of PF-06647020 as a single agent 
treatment on a Q2W dosing schedule.
•
Part 2: To evaluate the overall safety profile of PF-06647020 as a single agent and in 
combination with avelumab at Q2W dosing schedule in OVCA and NSCLC patients 
at the RP2D.
Secondary Objectives 
•
To characterize the single and multiple dose PK of ADC (PF-06647020), total 
antibody (hu6M024 mAb) and unconjugated payload (PF-06380101) when 
PF-06647020 administered alone or on combination with avelumab, and PK of 
avelumab.
•
To evaluate the immunogenicity as measured by presence of ADA in patients treated 
with PF-06647020 or PF-06647020 in combination with avelumab.
•
To evaluate anti-tumor activity of PF-06647020 as a single agent and when given in 
combination with avelumab in patients with OVCA and NSCLC.
 
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Primary Endpoints
•
Part 1: First Cycle DLTs for the dose escalation portion.  A cycle is 28 days in 
duration.
•
Part 2: AEs (as graded by NCI CTCAE v.4.03); laboratory abnormalities (as graded 
by NCI CTCAE v.4.03); vital signs (blood pressure, pulse rate); or 
electrocardiograms (ECGs).
Secondary Endpoints
•
Pharmacokinetics: PK parameters of PF-06647020, total antibody (hu6M024 mAb),
unconjugated payload (PF-06380101), and avelumab.  
•
Immunogenicity: Incidence of ADA and neutralizing antibodies (Nab) against 
PF-06647020 and avelumab.
•
Efficacy: OR, DoR, DCR, TTP, and PFS, as determined by Investigator [As assessed 
by RECIST version 1.1]. (Appendix 2).
 
 
 
 
 
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Study Design:
This is a Phase 1, open label, multi-center, non-randomized, multiple dose, safety, PK and 
pharmacodynamic study, initially designed to evaluate single agent PF-06647020 in 
sequential cohorts of adult patients with advanced solid tumors for whom no standard 
therapy is available.  Successive cohorts of patients received doses of PF-06647020
intravenously Q3W starting at a dose of 0.2 mg/kg. This study has been expanded for safety, 
PK, and efficacy evaluation of PF-06647020 following a Q2W dosing schedule as a single 
agent treatment in OVCA and NSCLC patients, as well as combined treatment of 
PF-06647020 with avelumab in OVCA patients.
Initial Design: Q3W Regimen (Original Protocol through Amendment 6)
This clinical study will include two parts.  Part 1 will estimate the MTD/RP2D in dose 
escalation cohorts in patients with advanced solid tumors unresponsive to currently available 
therapies or for whom no standard therapy is available.  Part 2 will include approximately 
87 patients enrolled at a RP2D selected by the Sponsor and Investigators from Part 1, to 
explore benefit from treatment and to better define the safety profile, as well as the RP2D.  
This expansion cohort will include approximately 22 patients with metastatic or recurrent 
TNBC, 45 patients with advanced epithelial ovarian cancer, primary peritoneal or fallopian 
tube cancer (OVCA) and 20 patients with advanced NSCLC. 
 
 
 
 
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A drug-drug interaction (DDI) sub-study for evaluating the effect of multiple-dose 
fluconazole on the PK of unconjugated payload (PF-06380101) is currently ongoing. The 
DDI sub-study is an open-label, 2-period, fixed sequence design in up to 10 patients to 
determine the effect of multiple-dose fluconazole, a model moderate CYP3A4 inhibitor, on 
the PK of PF-06380101 (payload), when fluconazole is co-administered with PF-06647020. 
This sub-study will be set up as a separate cohort from above mentioned studies in TNBC, 
NSCLC and OVCA, and the sub-study design and procedure details can be found in 
Appendix 7.
Current Q2W Regimen Expansion (Amendment 7)
The Q2W regimen expansion is designed to evaluate safety, PK and anti-tumor efficacy of a 
Q2W dosing schedule as a single agent treatment of PF-06647020 in patients with OVCA 
and NSCLC, and combined treatment of PF-06647020 with avelumab in OVCA patients.  If 
supported by safety and anti-tumor efficacy, additional combination study of PF-06647020 
with avelumab may also be investigated (eg, in approximately 24 patients with NSCLC).  
The study contains two parts, a Part 1 dose escalation to evaluate safety, PK and preliminary 
anti-tumor efficacy of PF-06647020 as a single agent treatment, and a Part 2 dose expansion 
to evaluate safety, PK and efficacy of PF-06647020 as single agent treatment and in 
combination with avelumab.
Part 1 contains a dose escalation scheme to estimate the MTD/RP2D of PF-06647020 as 
single agent treatment in patients with platinum-refractory or resistant OVCA and patients 
with recurrent NSCLC (in approximately 20 patients) using modified toxicity probability 
interval (mTPI) method.  Successive cohorts of patients will receive doses of PF-06647020
starting at a dose of 2.1 mg/kg, Q2W. Once a RP2D is determined and preliminary efficacy 
is observed, dose expansion (Part 2) will be started to further investigate safety, PK and 
efficacy of Q2W PF-06647020 in three cohorts of patients:
•
Cohort 1: PF-06647020 as a single agent treatment in patients with platinum resistant 
or refractory OVCA.
•
Cohort 2: PF-06647020 as a single agent treatment in patients with recurrent 
advanced NSCLC.
•
Cohort 3: PF-06647020 in combination with avelumab in platinum resistant or 
refractory OVCA.
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Approximately 24 patients will be enrolled for each cohort.  Patients that were enrolled in the 
Part 1 single agent dose escalation will be counted as part of the 24 patients in their 
respective Part 2 single agent cohorts. Additional cohorts (eg, approximately 24 patients 
with recurrent advanced NSCLC) receiving combination of PF-06647020 with avelumab 
may also be considered for inclusion at a later time, if supported by safety and anti-tumor 
activity observed in Cohort 2. 
In the combination expansion cohort(s), the RP2D of PF-06647020 as determined by Part 1 
will be used as the dose to combine with avelumab at 800 mg (both administered IV, Q2W).  
The PF-06647020 dose may be reduced (but not further escalated) for safety reasons. After 
at least 6 patients in the combination cohort have completed a minimum observation period 
of 4 weeks, safety will be reviewed by the investigators and Pfizer (using the same DLT 
definition described in Section A4.2). If there are no safety concerns precluding continuation 
of the study, enrollment of the remaining patients for this cohort will proceed. If DLT is 
observed in 2 out of 6 patients, at least 6 additional patients will be enrolled at a reduced dose 
of PF-06647020 (the reduced dose of PF-06647020 could be one dose level below the 
defined RP2D from Part 1 assuming the RP2D is above the starting dose of Part 1 
(ie, 2.1 mg/kg), or 1.8 mg/kg of PF-06647020 in a circumstance that the RP2D from Part 1 is 
2.1 mg/kg).
 
 
  
Approximately 190 patients are expected to be enrolled in the study at approximately
15-20 sites (including approximately 72 patients in the Q2W Regimen Sub-Study).  The 
actual number of patients enrolled will depend upon the tolerability of PF-06647020 and the 
number of dose levels required to identify the MTD/RP2D. 
Patients will participate in the study for approximately 6 months or until disease progression
(PD) as per RECIST 1.1 [or immune-related response evaluation criteria in solid tumors 
(irRECIST) in Cohort 3 of the Q2W regimen expansion], patient withdrawal of consent,
unacceptable toxicity occurs, patient loss to follow up, or the study is terminated by the 
Sponsor, whichever comes first.  This includes a 4 week screening period, a 4 month 
treatment period and a 4 week post dose follow-up period.  A follow-up visit within 4 weeks 
after the last dose of study drug for AE and serious adverse event (SAE) collection will be 
conducted.  The time on study can vary depending on the observed toxicity and potential 
benefit an individual patient derives.  The study is expected to be completed in 
approximately 36 months. 
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SCHEDULE OF ACTIVITIES (ORIGINAL Q3W REGIMEN) 
The schedule of activities table provides an overview of the protocol visits and procedures.  Refer to the Assessments section of the 
protocol for detailed information on each assessment required for compliance with the protocol. 
The investigator may schedule visits (unplanned visits) in addition to those listed on the schedule of activities, in order to conduct 
evaluations or assessments required to protect the well-being of the patient.
Visit Identifier
Screen/ 
Baseline1
(28 days)
Treatment Period
Post Treatment
Cycle 1 Only
(Days 1 to 21)
Cycle 2 and Subsequent Cycles
(Days 1 to 21)
Day 1
Day 4
(1)
Day 8
(1)
Day 15
(2)
Day 1
(2)
Day 8
(±2)
Day 15
(2)
End of 
Treatment29
(+7)
Follow 
Up30
(+7)
Informed Consent2
X
Tumor History3
X
Medical History4
X
Full Physical Examination5
X
X
X
Abbreviated Physical Examination
X
X
X
X
X
X
Ophthalmic Examination6
X
Baseline Signs and Symptoms7
X
Height
X
Weight8
X
X
X
Vital signs (BP/PR/Temp)9
X
X
X
X
X
X
X
X
X
X
ECOG Performance Status10
X
X
X
X
X
(12 lead) ECG11
X
X
X
X
X
X
Laboratory
Hematology12
X
X
X
X
X
X
X
X
X
Blood Chemistry13
X
X
X
X
X
X
X
X
X
Coagulation Panel14
X
X
X
Urinalysis15
X
X
X
X
Pregnancy test16
X
X
X
X
Registration and Treatment
Registration17
X
Study Treatment18
X
X
Tumor assessments 
CT or MRI scan or equivalent19
X
X (every 
6 weeks)
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Visit Identifier
Screen/ 
Baseline1
(≤28 days)
Treatment Period
Post Treatment
Cycle 1 Only
(Days 1 to 21)
Cycle 2 and Subsequent Cycles
(Days 1 to 21)
Day 1
Day 4
(±1)
Day 8
(±1)
Day 15
(±2)
Day 1
(±2)
Day 8
(±2)
Day 15
(±2)
End of 
Treatment29
(+7)
Follow 
Up30
(+7)
Other samplings 
 
 
 
CA-125 Serum Biomarker (OVCA 
only) 22
X
X (every 
6 weeks)
X
 
Blood Samples for PK24
See Pharmacokinetic, Immunogenicity and Biomarker Sampling Schedule Table below
Blood Sample for Immunogenicity 
Test (Anti-PF-06647020 Antibody)25
See Pharmacokinetic, Immunogenicity And Biomarker Sampling Schedule Table below
See Pharmacokinetic, Immunogenicity and Biomarker Sampling Schedule Table below
Other clinical assessments
Serious and non-serious adverse 
Event monitoring27
X
X
X
X
X
X
X
X
X
X
Concomitant treatments and 
non-drug supportive interventions28
X
X
X
X
X
X
X
X
X
X
Abbreviations: CT = computed tomography; ECG = electrocardiogram; MRI = magnetic resonance imaging; BP = blood pressure; PR = pulse rates;
PK = pharmacokinetics; ECOG = Eastern Cooperative Oncology Group; OVCA = Ovarian cancer
Unless otherwise specified, laboratory values and assessments should be obtained prior to the PF-06647020 infusion.  If the infusion is held, assessments should 
still be performed.  For Cycle 2 and subsequent cycles, complete blood count (CBC), blood chemistry, other laboratory tests and brief physical examinations, 
values/assessments should be obtained within 72 hours (ideally within 24 hours) prior to the PF-06647020 infusion and key values should be received and 
reviewed to ensure appropriate values for dosing. 
Footnotes
1.
Screening: To be conducted within 28 days prior to treatment start.
2.
Informed Consent: Must be obtained prior to undergoing any study specific procedures and may be >28 days from first dose.
3.
Tumor History: Will be collected within 28 days prior to treatment start.  Includes history of disease under study including details of primary diagnosis and 
treatment history. 
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4.
Medical History: Includes history of disease process other than the cancer under study (active or resolved) and concurrent illness.  Includes prior treatments 
and any current medical treatments for any condition.
5.
Full Physical Exam: No need to repeat full physical exam on Cycle 1 Day 1 (C1D1) if baseline assessment performed within one week prior to that date. 
6.
Ophthalmic Examination: An eye exam (performed by an ophthalmologist) will be performed at screening. The eye exam includes Best Corrected Visual 
Acuity (BCVA), Intraocular Pressure (IOP) preferably by Goldmann applanation, Biomicroscopic Exam (also called slit lamp exam) to evaluate the 
Lids/Lashes/Adnexae, conjunctiva/sclera, cornea, anterior chamber, iris, lens, and Dilate fundus exam to evaluate the optic nerve, the vessels, the macula, 
and the peripheral retina.  Further ophthalmic examinations should be guided by specific ocular signs and symptoms should they occur during treatment and 
follow up.
7.
Baseline Signs & Symptoms: On Day 1 prior to the start of study treatment, patients will be asked about any signs and symptoms experienced within the 
past 14 days of starting treatment.  Baseline signs and symptoms will be recorded on the Medical History Case Report Form (CRF) page.
8.
Weight: Will not be measured at each visit, however, patients should be monitored throughout the study for significant weight change.  If a patient’s weight 
fluctuates by more than 10% in either direction, weight should be collected to recalculate the appropriate dose for the next cycle.  In cases where individual
institution/pharmacy require more frequent weight measurements, weight can be obtained on each day of administration, and the dose recalculated.
9.
Vital signs: Includes blood pressure (BP), temperature (oral, tympanic or axillary) and pulse rate to be recorded in the sitting position after approximately 
5 minutes of rest.  On Day 1 of each cycle, vital signs should be measured prior to infusion start (pre-dose) and 1 hour after the start of the infusion. 
Beginning at Cycle 8, the Day 8 assessments will be optional for patients that have achieved a complete response (CR), partial response (PR) or stable 
disease (SD) if agreed upon by the treating physician.
10. Performance status: use Eastern Cooperative Oncology Group (ECOG) – see Appendix 3. 
11. 12 lead ECG (singlet): ECGs will be collected during Screening and at the End of Treatment visit.  Additional ECGs will be collected prior to dosing, at 
end of infusion and at Day 8 of each dose of study treatment.  When coinciding with blood sample draws for PK, ECG assessment should be performed prior 
to blood sample collection, such that the blood sample is collected at the nominal time.  If the mean QTc is prolonged (value of >500 msec), the ECGs 
should be re-evaluated by a qualified person at the institution for confirmation.  Additional ECGs should be performed as clinically indicated.  Beginning at 
Cycle 8, the Day 8 assessments will be optional for patients that have achieved a CR, PR or SD if agreed upon by the treating physician.
12. Hematology: No need to repeat on C1D1 if baseline assessment performed within 72 hours prior to that date.  See Assessments section for Laboratory Tests 
list.  Beginning at Cycle 8, the Day 8 assessments will be optional for patients that have achieved a CR, PR or SD if agreed upon by the treating physician.
13. Blood Chemistry: No need to repeat on C1D1 if baseline assessment performed within 72 hours prior to that date.  See Assessments section for Laboratory 
Tests list.  Beginning at Cycle 8, the Day 8 assessments will be optional for patients that have achieved a CR, PR or SD if agreed upon by the treating 
physician.
14. Coagulation: See Assessments section for Laboratory Tests list.
15. Urinalysis: Dipstick or full urinalysis is acceptable.  Microscopic analyses if dipstick abnormal.  If 2+ protein on urine dipstick, then collect spot urine 
sample to calculate urine protein to creatinine ratio (UPCR). See Assessments section for Laboratory Tests list.
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17. Registration: Patient number and dose level allocation will be provided by Pfizer Inc.
18. Study Treatment: PF-06647020 will be administered once every 21 days as an IV infusion over approximately 60 minutes. 
19. Tumor Assessments: Tumor assessments will include all known or suspected disease sites and may include chest, abdomen and pelvis CT or MRI scans.  
Brain scans and bone scans will be performed at baseline if disease is suspected and on-study as appropriate to follow disease.  Baseline central nervous 
system (CNS) imaging is not required with the exception of symptomatic patients to rule out CNS metastases.  CT or MRI scans are to be done every 
6 weeks (±5 days) from the start of study treatment until disease progression by RECIST (v1.1) or death, or at the time of withdrawal from treatment (if not 
done in the previous 6 weeks).  The frequency may be reduced to every 12 weeks after 6 months of study treatment.  Tumor assessments should be fixed 
according to the calendar, regardless of treatment delays.  For patients enrolled in Part 2, responses of CR or PR must be confirmed by repeat assessment no 
less than 4 weeks after the criteria for response are first met.  Tumor assessments should be repeated at the End of Treatment visit if more than 6 weeks have 
passed since the last evaluation. All radiographic images will be collected for potential central review. Additional information on diagnostic imaging 
procedures and collection will be included in the Imaging Manual.
 
 
 
 
 
 
 
 
 
22. CA-125 Serum Biomarker: Ovarian cancer patients only.  Samples should be collected at pre-treatment, each tumor assessment (every 6 wks), and end of 
treatment.  Additional serum samples to be collected for assessment of CA-125 as per Investigator discretion.
 
24. PK Sampling: Specific timing for collection of serum pharmacokinetic samples can be found in the Pharmacokinetic, Immunogenicity and Biomarker Sampling 
Schedule table below.
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25. Immunogenicity Sample: Specific timing for collection of anti-PF-06647020 antibody samples can be found in the Pharmacokinetic, Immunogenicity and 
Biomarker Sampling Schedule schedule table below. 
 
 
27. Adverse Event (AE) Assessments: AEs should be documented and recorded at each visit using NCI CTCAE version 4.03.  The time period for actively 
eliciting and collecting AEs and SAEs (“active collection period”) for each patient begins from the time the patient provides informed consent through and 
including a minimum of 28 calendar days after the last investigational product administration.  If the patient begins a new anticancer therapy, the period for 
recording non-serious AEs on the CRF ends at the time the new treatment is started.  However, any SAEs occurring during the active collection period must 
still be reported to Pfizer Safety and recorded on the CRF, irrespective of any intervening treatment. Beginning at Cycle 8, the Day 8 assessments will be 
optional for patients that have achieved a CR, PR or SD if agreed upon by the treating physician.
28. Concomitant Treatments and Non Drug Supportive Interventions: All prior/concomitant medications within 28 days (4 weeks) prior to first dose of 
study treatment should be recorded in the CRF including supportive care drugs (eg, anti-emetic treatment and prophylaxis), and the drugs used to treat 
adverse events or chronic diseases, and non-drug supportive interventions (eg, transfusions). Beginning at Cycle 8, the Day 8 assessments will be optional 
for patients that have achieved a CR, PR or SD if agreed upon by the treating physician.
29. End of treatment visit: Conducted at the visit that the patient is discontinued from the trial.  Assessments should be obtained if not completed in the last 
week.  Complete tumor assessments if not completed in the last 6 weeks. 
30. Follow up: At least 28 days and no more than 35 days after end of treatment visit, patients will return to undergo review of concomitant medications, vital 
signs, and assessment for resolution of any treatment related toxicity.  Patients continuing to experience toxicity at this point following discontinuation of 
treatment will continue to be followed at least every 4 weeks until resolution or determination, in the clinical judgment of the Investigator, that no further 
improvement is expected. 
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Pharmacokinetic, Immunogenicity and Biomarker Sampling Schedule (Q3W Regimen)
Protocol Activity
Screen 
(≤28 days)
Treatment Period
EOT 
(+7)
Cycle 1 Only
(Days 1 to 21)
Cycles
2 and 3
Cycle 4
Every Cycle 
Thereafter
Day 1
Day 2 Day 4
(±1)
Day 8
(±1)
Day 
15
(±2)
Day 1
Day 1
Day 
2
Day 
4
(±1)
Day 8
(±1)
Day 
15
(±2)
Day 1
Pre-dose* 1 hr*4 hr*
24
hr*
Pre-dose* 1 hr*Pre-dose* 1 hr* 4 hr*
24
hr*
Pre-dose*
1 hr*
Blood Samples for 
PF-063801011
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Blood Samples for 
PF-06647020 and 
hu6M024 mAb2
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Blood Sample for 
Immunogenicity Test 
(Anti-PF-06647020 Antib
ody)3
X
X
X
X
X
X
 
 
 
 
 
*Sampling times are related to the start of infusion; 1 hr samples should be collected immediately before the infusion ends. All samples obtained within 10% of the nominal time 
(eg, within 6 minutes of a 60 minute sample) will be considered protocol compliant, and the exact time of the sample collection will always be noted on the CRF.
Footnotes
1.
Blood sample for PF-06380101: 4 ml of whole blood will be collected for PK analysis of unconjugated payload (PF-06380101).
2.
Blood sample for PF-06647020 and hu6M024 mAb: 6 ml of whole blood will be collected for PK analysis of ADC (PF-06647020) and total antibody (hu6M024 mAb).
3.
Blood sample for immunogenicity test: Blood samples (6 mL) for immunogenicity testing against PF-06647020 will be collected.  Collection of serum to detect the 
presence of antibodies to PF-06647020 is to be obtained prior to the start of treatment.  Patients having an unresolved adverse event that is possibly related to 
anti-PF-06647020 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 
adverse event or its sequelae resolve or stabilize at a level acceptable to the investigator and sponsor.
 
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TABLE OF CONTENTS
PROTOCOL SUMMARY.......................................................................................................11
SCHEDULE OF ACTIVITIES (ORIGINAL Q3W REGIMEN)............................................21
LIST OF TABLES...................................................................................................................31
LIST OF FIGURES .................................................................................................................32
APPENDICES .........................................................................................................................33
1. INTRODUCTION ...............................................................................................................34
1.1. Indication.................................................................................................................34
1.2. Background and Rationale ......................................................................................34
..........................................................35
1.2.2. Nonclinical Pharmacokinetics ....................................................................41
1.2.3. Nonclinical Safety ......................................................................................42
1.2.4. Clinical Safety (PF-06647020)...................................................................43
1.2.4.1. Pharmacokinetics (PF-06647020).............................................47
1.2.4.2. Efficacy in Patients treated with PF-06647020.........................47
1.3. Starting Dose Rationale...........................................................................................48
1.4. PTK7 Immunohistochemistry (IHC) Assay for PTK7 Expression.........................48
1.5. Triple Negative Breast Cancer, NSCLC and OVCA in Dose Expansion...............50
1.6. Rationale for Expansion of OVCA Cohort (Protocol Amendment 5) ....................50
1.7. Rationale for DDI Sub-Study..................................................................................50
2. STUDY OBJECTIVES AND ENDPOINTS.......................................................................51
2.1. Objectives................................................................................................................51
2.1.1. Objectives – Dose Escalation (Part 1) ........................................................51
2.1.2. Objectives – Dose Expansion (Part 2)........................................................51
2.2. Endpoints.................................................................................................................52
2.2.1. Endpoints – Part 1.......................................................................................52
2.2.2. Endpoints – Part 2.......................................................................................53
3. STUDY DESIGN.................................................................................................................54
3.1. Study Overview.......................................................................................................54
3.2. Dose Escalation Phase (Part 1)................................................................................55
3.3. DLT Definition........................................................................................................57
3.4. MTD Definition.......................................................................................................59
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3.5. Dose Expansion Phase (Part 2) ...............................................................................59
3.6. Recommended Phase 2 Dose (RP2D) Definition ...................................................59
4. PATIENT SELECTION......................................................................................................59
4.1. Inclusion Criteria.....................................................................................................59
4.2. Exclusion Criteria....................................................................................................63
4.3. Lifestyle Guidelines ................................................................................................64
4.4. Sponsor’s Qualified Medical Personnel..................................................................66
5. STUDY TREATMENTS.....................................................................................................66
5.1. Allocation to Treatment ..........................................................................................66
5.2. Patient Compliance .................................................................................................67
5.3. Drug Supplies..........................................................................................................67
5.3.1. Dosage Form and Packaging ......................................................................67
5.3.2. Preparation and Dispensing........................................................................68
5.4. Administration.........................................................................................................68
5.4.1. Recommended Dose Modifications............................................................69
5.4.2. Dose Interruptions/Delays ..........................................................................69
5.4.3. Dose Reductions .........................................................................................70
5.5. Drug Storage ...........................................................................................................72
5.6. Drug Accountability................................................................................................72
5.6.1. Destruction of Investigational Product Supplies ........................................72
5.7. Concomitant Treatment(s).......................................................................................73
5.7.1. Other Anti-tumor/Anti-cancer or Experimental Drugs...............................73
5.7.2. Supportive Care ..........................................................................................74
5.7.3. Hematopoietic Growth Factors...................................................................74
5.7.4. Anti Diarrhea, Anti-Emetic Therapy..........................................................74
5.7.5. Anti-inflammatory Therapy........................................................................74
5.7.6. Corticosteroids............................................................................................74
5.7.7. Surgery........................................................................................................74
6. STUDY PROCEDURES .....................................................................................................75
6.1. Screening.................................................................................................................75
6.2. Treatment Period.....................................................................................................75
6.3. Follow-up Visit .......................................................................................................75


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6.4. Patient Withdrawal..................................................................................................75
7. ASSESSMENTS..................................................................................................................77
7.1. Safety Assessment...................................................................................................78
7.1.1. Pregnancy Testing ......................................................................................78
7.1.2. Adverse Events...........................................................................................78
7.1.3. Laboratory Safety Assessment ...................................................................78
7.1.4. Vital Signs and Physical Examination........................................................79
7.1.5. (12-Lead) ECG ...........................................................................................80
7.2. Pharmacokinetics Assessments...............................................................................81
7.2.1. Serum Sample Collection for PK analysis of ADC (PF-06647020), 
Total Antibody (hu6M024 mAb) and Unconjugated Payload 
(PF-06380101).................................................................................................81
..........................................................................................81
...........................................................................................81
....................................................................................82
7.4. Tumor Response Assessments ................................................................................82
.....................................................82
..................................................................83
7.5.2. Immunophenotyping...................................................................................83
.............................................................84
7.7. Immunogenicity Assessment...................................................................................84
.............................................................................................85
.........................................................................85
....................................................................................86
7.9. Other Assessments ..................................................................................................86
7.9.1. Tumor and Medical History........................................................................86
7.9.2. Baseline Signs and Symptoms....................................................................86
8. ADVERSE EVENT REPORTING......................................................................................87
8.1. Adverse Events........................................................................................................87
8.1.1. Reporting Period.........................................................................................87
8.1.2. Definition of an Adverse Event ..................................................................87
8.2. Medication Errors....................................................................................................88
8.2.1. Abnormal Test Findings .............................................................................89
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8.2.2. Serious Adverse Events ..............................................................................89
8.2.3. Protocol-Specified Serious Adverse Events ...............................................90
8.2.4. Potential Cases of Drug-Induced Liver Injury............................................90
8.2.5. Hospitalization............................................................................................91
8.3. Severity Assessment................................................................................................92
8.3.1. Causality Assessment .................................................................................92
8.3.1.1. Exposure During Pregnancy......................................................93
8.3.1.2. Occupational Exposure .............................................................94
8.4. Withdrawal Due to Adverse Events (See also the Section on Patient 
Withdrawal)...............................................................................................................94
8.4.1. Eliciting Adverse Event Information..........................................................94
8.5. Reporting Requirements..........................................................................................95
8.5.1. Serious Adverse Event Reporting Requirements .......................................95
8.5.2. Non Serious Adverse Event Reporting Requirements................................95
8.5.3. Sponsor’s Reporting Requirements to Regulatory Authorities ..................95
9. DATA ANALYSIS/STATISTICAL METHODS...............................................................96
9.1. Analysis sets............................................................................................................96
9.2. Statistical Methods and Properties ..........................................................................97
9.2.1. Statistical Methods for Dose Escalation/De-Escalation .............................97
9.2.2. Statistical Method for Estimating the MTD ...............................................98
9.3. Sample Size Determination.....................................................................................99
9.4. Efficacy Analysis ....................................................................................................99
9.4.1. Analysis of Overall Response.....................................................................99
9.5. Analysis of Other Endpoints .................................................................................100
9.5.1. Analysis of Pharmacokinetics...................................................................100
9.5.2. Pharmacokinetic/Pharmacodynamic Analysis..........................................100
9.5.3. Analysis of Immunogenicity Data............................................................101
9.6. Safety Analysis......................................................................................................101
9.6.1. Analysis of Primary Endpoint ..................................................................101
9.6.2. Analysis of Secondary Safety Endpoints..................................................102
9.6.2.1. Adverse Events........................................................................102
9.6.2.2. Laboratory Tests Abnormalities..............................................102


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9.6.3. ECG ..........................................................................................................102
9.7. Data Safety Monitoring Committee ......................................................................103
10. QUALITY CONTROL AND QUALITY ASSURANCE...............................................103
11. DATA HANDLING AND RECORD KEEPING ...........................................................104
11.1. Case Report Forms/Electronic Data Record .......................................................104
11.2. Record Retention.................................................................................................104
12. ETHICS............................................................................................................................105
12.1. Institutional Review Board (IRB)/Ethics Committee (EC).................................105
12.2. Ethical Conduct of the Study ..............................................................................105
12.3. Patient Information and Consent.........................................................................105
12.4. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH 
GCP .........................................................................................................................106
13. DEFINITION OF END OF TRIAL.................................................................................106
13.1. End of Trial in All Participating Countries .........................................................106
14. SPONSOR DISCONTINUATION CRITERIA ..............................................................106
15. PUBLICATION OF STUDY RESULTS........................................................................107
15.1. Communication of Results by Pfizer ..................................................................107
15.2. Publications by Investigators ..............................................................................107
16. REFERENCES ................................................................................................................109
LIST OF TABLES
Table 1.
Summary of In Vivo Pharmacology Studies with PF-06647020 .........................38
Table 2.
Most Frequently Reported (Incidence 10%) Treatment Related Treatment 
Emergent Adverse Events (TEAEs) (Any Grade)................................................44
Table 3.
Most Frequently Reported (in 2 Patients) Grade 3 Treatment Related 
TEAEs...................................................................................................................44
Table 4.
Serious TEAEs Considered Treatment-Related by Investigator ..........................45
Table 5.
Patients Withdrawn From Study Due to TEAEs and Relationship with 
PF-06647020.........................................................................................................45
Table 6.
Most Frequently Reported (Incidence 10%) Treatment-Related TEAEs in 
OVCA Patients Treated at 2.8 mg/kg PF-06647020 (Any Grade).......................46
Table 7.
Most Frequently Reported (Incidence 10%) Treatment-Related TEAEs in 
NSCLC Patients Treated at 2.8 mg/kg PF-06647020 (Any Grade) .....................46
Table 8.
Dose Escalation Table ..........................................................................................56


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Table 9.
Table of Potential Dose Levels.............................................................................56
Table 10.
Dose Modifications for Toxicity Considered Possibly Drug-Related..................71
Table 11.
Pharmacodynamic Summary................................................................................83
Table 12.
Escalation Probability...........................................................................................98
Table 13.
Safety QTcF........................................................................................................102
Table 14.
Drugs Which may Have Clinically Significant Drug Interactions When 
Administered With Fluconazole1........................................................................133
Table 15.
Most Frequently Reported (Incidence 10% in the Pooled Expansion 
Cohort) Treatment-Emergent Adverse Events (TEAEs) in the Pooled 
Expansion Cohort (Any Grade)..........................................................................145
Table 16.
Most Frequently Reported (in 5 Patients in the Pooled Expansion Cohort) 
Grade 3 Treatment-Related TEAEs in the Pooled Expansion Cohort .............145
Table 17.
Avelumab Treatment Related Adverse Events (Incidence 5%) in the 
OVCA Cohort.....................................................................................................148
Table 18.
Table of Potential Dose Levels*.........................................................................154
Table 19.
Avelumab: Treatment Modifications for Symptoms of Infusion-related 
Reactions.............................................................................................................173
Table 20.
Avelumab: Management of Immune-related Adverse Events............................175
Table 21.
PF-06647020 Dose Modifications......................................................................179
Table 22.
PF-06647020-Avelumab Combination: Treatment Modification for 
Neutropenia.........................................................................................................180
Table 23.
Overall Response Derived from Changes in Index, Non-index and New 
Lesions................................................................................................................194
LIST OF FIGURES
Figure 1.
PTK7 Expression in the Preclinical Tumor Models.............................................37
Figure 2.
Tumor Growth Curves for PF-06647020 Nonclinical Studies.............................40
Figure 3.
PTK7 H-scores in NSCLC, Breast and Ovarian Cancers.....................................49


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APPENDICES
Appendix 1. Abbreviations....................................................................................................112
Appendix 2. RECIST (Response Evaluation Criteria In Solid Tumors) version 
1.1 Guidelines.....................................................................................................116
Appendix 3. ECOG Performance Status................................................................................121
Appendix 4. National Cancer Institute (NCI) Common Terminology Criteria for 
Adverse Events (CTCAE) ..................................................................................122
Appendix 5. Management of Infusion Related Reactions Including Allergic Reactions, 
Cytokine Release Syndrome or Anaphylaxis .....................................................123
Appendix 6. Potent CYP3A Inhibitors and Inducers.............................................................125
Appendix 7. Drug-Drug Interaction (DDI) Sub-Study..........................................................126
Appendix 8. Q2W Regimen Expansion Sub-Study (Single Agent PF-06647020 and 
Combination of PF-06647020 with Avelumab in patients with OVCA and 
NSCLC)..............................................................................................................142
Appendix 9. Immune-related Response Criteria Derived from RECIST 1.1 (irRECIST) ....193


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1. INTRODUCTION
1.1. Indication
PF-06647020 is an antibody-drug conjugate (ADC) against the PTK7 (Protein Tyrosine 
Kinase 7) tumor antigen.  It is intended to be used for the treatment of adult patients with 
advanced solid tumors unresponsive to currently available therapies, or for whom no 
standard therapy is available.
1.2. Background and Rationale
ADCs were developed to improve the therapeutic indices of cytotoxic anti-cancer agents.  
The strategy makes use of an immunoconjugate in which a cytotoxic agent is chemically or 
enzymatically linked to an antibody that selectively binds to an internalizing 
tumor-associated antigen. This strategy allows specific delivery of the cytotoxic agent to the 
tumor site while minimizing the exposure to normal tissues.
PF-06647020 is an anti-PTK7 ADC intended to be for the treatment of patients with cancer.  
PF-06647020 is comprised of a humanized anti-PTK7 monoclonal antibody (mAb) linked to 
an auristatin (Aur0101) via a cleavable cysteine-reactive linker.  Auristatins are fully 
synthetic dolastatin-based pentapeptide inhibitor of tubulin polymerization that induce G2/M 
cell cycle arrest and cell death at low picomolar intracellular concentrations.13,14
PTK7 is a phylogenetically conserved member of the pseudokinase family of receptor 
tyrosine kinases (RTKs) with no observable kinase activity.4  Genetic and biochemical 
studies in multiple organisms have demonstrated a key function for PTK7 in planar cell 
polarity via the Wnt-pathway signaling, and PTK7-deficient embryos have developmental 
defects.3,7,11  In addition, PTK7 promotes cell survival in colorectal cancer and acute myeloid 
leukemia (AML), and PTK7 may promote resistance to chemotherapy in AML.9,12
Bioinformatics and literature analysis have revealed that PTK7 mRNA expression levels in 
many types of tumors are higher than corresponding normal tissues including bladder, brain, 
breast, colorectal, gastric, kidney, liver, lung, pancreatic and skin cancer.  In addition, 
PTK7 was found to be enriched in cancer stem cells (CSCs), also known as tumor-initiating 
cells, harvested from patient-derived xenografted tumor models of triple negative breast 
cancer (TNBC) and non-small cell lung cancer (NSCLC) in preclinical studies (unpublished 
data).  It was also reported that positive expression of PTK7 is linked to poor prognosis in 
patients with NSCLC (Pfizer internal data) and TNBC who received chemotherapy, 
particularly in a subgroup patient population who received anthracycline treatment.2  In 
preclinical studies, PF-06647020 induced sustained tumor regressions in models of ovarian 
cancer (OVCA), NSCLC and TNBC.19
For complete details of the in vitro and nonclinical studies, refer to PF-06647020 
Investigator’s Brochure (IB).22
TNBC accounts for 15% to 20% of breast cancers and is diagnosed based on lack of ER and 
PgR expression by IHC and of HER2 over expression or gene amplification by IHC or in situ 
hybridization, respectively.  TNBC is a heterogeneous disease, not only on the molecular 
level, but also on the pathologic and clinical levels.  The majority of patients with TNBC 


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respond with high sensitivity to chemotherapies including anthracyclines and taxanes in the 
neoadjuvant or adjuvant settings.  However, TNBC is associated with a significantly higher 
probability of relapse and poor OS in the first few years after diagnosis compared with other 
breast cancer subtypes.  Positive expression of PTK7 in TNBC was observed in ~84% of 
archived samples surveyed using a research grade IHC assay sets tested (Pfizer internal data).
NSCLC accounts for approximately 85% cases of lung cancer, the leading cause of 
cancer-related mortality in the United States (US) and worldwide.  Most patients with 
NSCLC have locally advanced and distant metastatic disease (stage III/IV) at the time of 
presentation, which is associated with a poor prognosis with 5-year OS rate less than 10%.  
Although targeted therapies (eg, Erlotinib and Crizotinib) for patients with NSCLC whose 
tumors carry EGFR mutation or are ALK-positive and promising immunotherapies are being 
developed, the unsatisfactory treatment outcomes in advanced NSCLC highlights the need of 
novel alternative therapies. In addition, PTK7 expression in NSCLC was observed to cover a 
dynamic range (Pfizer internal data), suggesting that patient selection by PTK7 expression 
levels may identify patients that may be more likely to benefit. This is the first in human 
study of PF-06647020 in patients with advanced solid tumors, unresponsive to existing 
therapies, or for whom no standard treatment is available.
OVCA is the 6th most common malignancy in developed countries with approximately 
100,000 new cases resulting in nearly 65,000 deaths per year.15 Patients are typically treated 
with surgery followed by chemotherapy.  Initial therapy consists of combinations with 
platinum-containing agents which results in responses in 70-80% of patients.  However, the 
disease relapses in almost all patients requiring further therapy.  The timing of the relapse 
from the end of the platinum-containing regimen has been shown to be prognostic with 
platinum-resistant tumors (defined as progression while receiving initial therapy or relapse 
<6 months from end of initial regimen), as having the worst outcomes.16 Pegylated 
doxorubicin and topotecan are both indicated as single agents in patients with refractory 
OVCA.  In patients with platinum-resistant disease, both of these compounds result in RR of 
10-15%, PFS of 14 weeks, and OS 35-40 weeks highlighting the need for alternative 
therapies.16
 
 
 
 
  
 
 
 
 
 
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1.2.2. Nonclinical Pharmacokinetics
Following a single IV or intraperitoneal (IP) dose of PF-06647020 to nod/SCID mice, 
systemic exposure of ADC and total Ab were similar.  After repeat IV dosing of 
PF-06647020 to Wistar Han rats and cynomolgus monkeys, mean systemic exposure (as 
assessed by Cmax and area under the curve [AUC]) increased with increasing dose for ADC, 
total Ab, and unconjugated Aur0101 and no sex-related differences were observed.  Further, 
mean Cmax and AUC504 ratios on Day 22 relative to Day 1 were generally similar with ratios 
(Day 22/Day 1) less than 2.0 for ADC, total Ab, or unconjugated payload.  In addition, the 
mean systemic exposure of ADC and total Ab were similar.
In Wistar Han rats, the incidence of ADA induction to PF-06647020 was highest in the 
12 mg/kg/dose group (22% in toxicokinetic animals).  In general, serum concentrations in
most ADA-positive rats were similar to ADA-negative rats.  In cynomolgus monkeys, the 
incidence of ADA induction to PF-06647020 ranged from 75% to 93% across all dose groups 
(0.5, 2, and 4 mg/kg/dose).  On Study Day 1, systemic exposure in ADA-positive animals 
was similar to that of ADA-negative animals; whereas, on Study Day 22 systemic exposure 
in ADA-positive animals was lower than ADA-negative animals. 
After an IV dose of Aur0101 payload at 20 g/kg to Wistar Han rats, Aur0101 exhibited a 
mean systemic clearance (CL) of 70 mL/min/kg and a volume of distribution (Vss) of 
14,700 mL/kg, resulting in a terminal elimination half-life (t½) of approximately 6 hours. 
Following repeat IV dosing of Aur0101 to Wistar Han rats, mean systemic exposure 
increased with increasing dose.  Mean Cmax and AUC336 ratios on Day 29 relative to 
Day 1 were generally similar with ratios (Day 29/Day 1) less than 2.0, suggesting there was 
no accumulation of Aur0101 observed over the dosing interval.
Aur0101 was moderately to highly bound to plasma proteins (monkey < rat and human 
plasma proteins).  In vitro studies with non-radiolabeled compound suggest that 
Aur0101 preferentially distributes into human plasma relative to whole blood.  In vitro 
studies indicate that Aur0101 is a P-glycoprotein (P-gp) substrate.
Based on preliminary in vitro and in vivo assessments, Aur0101 is the only released chemical 
species resulting from PF-06647020 following incubation with rat, monkey, and human liver 
S9 or in rat and monkey serum after IV administration of PF-06647020.  A preliminary 
assessment of the metabolism of Aur0101 using non-radiolabeled compound was conducted 
using rat, monkey and human liver S9 fractions and human recombinant cytochrome 
P450 (rCYP) enzymes.  All metabolites were oxidative in nature and -Nicotinamide adenine 
dinucleotide phosphate (NADPH)-dependent with no amide hydrolysis products or 
glucuronide conjugates observed.  There was no evidence of human specific metabolites.  
Initial reaction phenotyping experiments suggest that CYP3A4 is the predominant enzyme 
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Based on the in vitro direct inhibition, metabolism-dependent inhibition, and induction data 
and the anticipated low systemic concentrations in humans (Cmax <0.001 M or 
<0.001 µg/mL, based on the assumption that levels of released Aur0101 are the same in 
humans as in monkeys), Aur0101 has an anticipated low probability to perpetrate 
pharmacokinetic DDI with compounds for which CYP (1A2, 2B6, C8, 2C9, 2C19, 2D6, 
and/or 3A4/5)-mediated metabolism constitutes the primary mechanism of clearance.  
However, since Aur0101 is primarily metabolized by CYP3A4, there is a potential that its 
metabolism may be altered in the presence of a potent inhibitor or inducer of CYP3A4. In 
addition, coadministration with a potent CYP3A4 inducer would result in accelerating 
clearance and lowering systemic Aur0101 concentrations.
1.2.3. Nonclinical Safety 
The nonclinical safety profile of PF-06647020 was characterized in a series of nonclinical in 
vivo studies. Repeat-dose exploratory and pivotal (Good Laboratory Practice (GLP) 
compliant) studies were conducted in Wistar Han rats and cynomolgus monkeys. An in vivo 
micronucleus assay was conducted in the rat pivotal toxicity study and safety pharmacology 
assessments (cardiovascular function in particular) were included in the monkey pivotal 
toxicity study. In addition, a GLP tissue cross-reactivity study was conducted with normal 
tissues of cynomolgus monkeys and humans. The major clinically significant findings in the 
repeat-dose toxicity studies were reversible bone marrow toxicity (all lineages) with 
associated hematological changes in both rats and monkeys. PF-6647020 was positive in the 
rat micronucleus assay and there were no adverse findings in the monkey cardiovascular 
function assessments.
Wistar Han rats were dosed with PF-06647020 once every 3 weeks for 3 cycles at 2, 6 or 
12 mg/kg/dose in an exploratory study and the pivotal GLP study. In the pivotal rat study, 
administration of 12 mg/kg/dose resulted in the early euthanasia of 2/30 animals on 
Days 8 and 9 due to poor clinical condition (eg decreased activity and skin turgor, gasping, 
lame/limping, chromodacryorrhea), which was secondary to bone marrow and lymphoid 
depletion associated with secondary bacterial infection. Major effects in surviving animals 
consisted of reversible bone marrow hypocellularity (minimal to mild at 2 mg/kg/dose and 
moderate to severe at 6 mg/kg/dose) that was associated with hematological changes of 
transient decreases in all major blood cell types. Additional adverse changes were noted in 
the testes (tubular degeneration) at 2 mg/kg/dose, thymus at 6 mg/kg/dose (lymphoid 
depletion) and skin (intraepidermal vesicle/cleft formation) at 12 mg/kg/dose. Other 
non-adverse changes (based on the small magnitude of the findings) consisted of increased 
mitoses and/or single cell necrosis in a variety of organs at 2 mg/kg/dose, connective tissue 
inflammation around various organs at 6 mg/kg/dose and mammary gland atrophy in males 
at 12 mg/kg/dose. Lastly, adverse injection site findings were seen at all doses and 
considered mostly related to extravasation of the test article. All changes, with the exception 
of the testicular findings, were fully recovered at the end of the 6-week reversibility period.  
The severely toxic dose for 10% of the animals (STD10) (was considered be 6 mg/kg/dose in 
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Cynomolgus monkeys were dosed with PF-06647020 once every 3 weeks for 3 cycles at 
0.5, 2 or 5 mg/kg/dose in an exploratory study and at 0.5, 2 or 4 mg/kg/dose in a pivotal 
study. In the exploratory study, administration of 5 mg/kg/dose resulted in the early 
euthanasia of 1/6 animals on Day 49 (6 days after the last dosing) due to lameness and 
swelling of the left hind limb, which correlated with microscopic findings of necrosis and 
inflammation at the injection site consistent with extravasation of the test article. Similar 
clinical and microscopic injection site findings were observed in other animals at 
2 mg/kg/dose. Test article-related effects were seen in the bone marrow (multifocal 
hematopoietic necrosis, altered myeloid to erythroid ratio) at 2 mg/kg/dose and lymphoid 
organs (lymphoid depletion) and testes (tubular degeneration) at 0.5 mg/kg/dose. In the 
pivotal monkey study, mild transient clinical signs (eg focal erythema or swelling, decreased 
activity, ataxia, emesis) consistent with a mild infusion reaction were observed in some 
animals at 2 mg/kg/dose and were possibly related to ADA formation. Clinical signs were 
noted within 5-60 min after the 2nd or 3rd dosing and were resolved by 4.5 hours post 
dosing. The most significant hematology changes in these monkeys consisted of minimal to 
marked transient decreases in neutrophil counts at 0.5 mg/kg/dose, which were most 
prominent at mid-cycle (eg, 10 days after dosing) and were considered adverse at 
4 mg/kg/dose based on the magnitude of the changes. Additional non-adverse hematology 
changes consisted of minimal to mild decreases in RBC mass parameters 2 mg/kg/dose.
Hematology changes were attributable to bone marrow toxicity and associated with altered 
myeloid to erythroid ratio. Other microscopic findings consisted of non-adverse minimally 
increased mitoses and/or single cell necrosis in several organs at 4 mg/kg/dose. Hematology 
and histology changes were recovered at the end of the 6-week reversibility period. It is 
noteworthy that, due to a change in dosing procedure (post-dose flushing), there were no 
clinical signs or microscopic findings of test article extravasation at the injection sites in the 
pivotal monkey study. Last, there were no test article-related effects on electrocardiograms 
and heart rate. The highest non-severely toxic dose (HNSTD) was considered to be 
4 mg/kg/dose in the pivotal monkey study.
The tissue cross-reactivity study conducted with PF-06647020 indicated membrane 
expression of PTK7 in the esophagus (squamous epithelium), cervix (squamous epithelium), 
and skin (epidermis, hair follicle and/or sweat glands) in monkeys and humans.  However, no 
test article related clinical and microscopic findings were observed in these organs in the 
Cynomolgus pivotal study. 
Overall, the nonclinical safety profile of PF-06647020 has been adequately characterized and 
supports its use in advanced cancer patients.
1.2.4. Clinical Safety (PF-06647020)
As of 17 March 2017, 112 patients have been treated with PF-06647020 Q3W, including
0.2, 0.5, and 1.25 mg/kg (2 patients at each dose level), 4 patients at 2.1 mg/kg, 96 patients at 
2.8 mg/kg, and 6 patients at 3.7 mg/kg.  Of the 112 patients treated, 40 (36%) experienced at 
least 1 Grade 3 treatment-related Treatment Emergent Adverse Event (TEAE), and 
95 patients (85%) had treatment-related TEAEs (regardless of grade).


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The most frequent reported (incidence 10%) treatment-related TEAEs (any grade) are 
summarized in Table 2.  The most frequently reported (in 2 patients) Grade 3 
treatment-related TEAEs are presented in Table 3.
Table 2.
Most Frequently Reported (Incidence 10%) Treatment Related 
Treatment Emergent Adverse Events (TEAEs) (Any Grade)
MedDRA PT
n (% in total n=112 patients)
Number of patients with at least 1 TEAE
95 (84.8)
Nausea
50 (44.6)
Alopecia
45 (40.2)
Fatigue
40 (35.7)
Headache
36 (32.1)
Neutropenia
32 (28.6)
Vomiting
28 (25.0)
Arthralgia
18 (16.1)
Decreased appetite
18 (16.1)
Diarrhea
17 (15.2)
Peripheral sensory neuropathy
16 (14.2)
Myalgia
15 (13.4)
Anemia
12 (10.7)
Source: Table 14.3.1.3.11.4
Table 3.
Most Frequently Reported (in 2 Patients) Grade 3 Treatment Related 
TEAEs
MedDRA PT
n (% in total n=112 patients)
Number of patients with at least 1 TEAE
50 (44.6)
Neutropenia
26 (23.0)
Headache
5 (4.5)
Vomiting 
4 (3.6)
Fatigue
3 (2.7)
Anemia
3 (2.7)
Febrile neutropenia
3 (2.7)
Lymphopenia
3 (2.7)
White blood cell count decreased
3 (2.7)
Myalgia
2 (1.8)
Stomatitis
2 (1.8)
Aspartate aminotransferase increased
2 (1.8)
Thrombocytopenia
2 (1.8)
Source: Table 14.3.1.3.11.4
Overall, 33 of the 112 patients (29.5%) treated had serious TEAEs (not considered treatment 
related).  Seven patients (6.3%) died while on study, of which 5 patients (4.9%) primary 
cause of death was attributed to disease progression, 1 patient experienced respiratory arrest 
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Twelve serious TEAEs considered treatment-related by the Investigator were reported for 
10 patients (8.9%) and is summarized in Table 4.  
Table 4.
Serious TEAEs Considered Treatment-Related by Investigator
MedDRA PT
n (% in total n=112 patients)
Grade 3 Febrile neutropenia
3 (2.7)
Grade 3 Abdominal pain
1 (1)
Grade 2 Constipation
1 (1)
Grade 3 Drug-induced liver injury
1 (1)
Grade 2 Headache
1 (1)
Grade 3 Neutropenia
1 (1)
Grade 4 Neutropenia
1 (1)
Grade 3 Stomatitis
1 (1)
Grade 2 Vomiting
1 (1)
Grade 3 Vomiting
1 (1)
Source: Table 16.2.7.1
Five (5) patients (4.9%) treated on study withdrew permanently from trial treatment due to 
TEAE and is summarized in Table 5.  
Table 5.
Patients Withdrawn From Study Due to TEAEs and Relationship with 
PF-06647020  
MedDRA PT
Relationship with PF-06647020
Grade 2 Pruritus
Related
Grade 2 Fatigue
Related
Grade 3 Fatigue
Related
Grade 4 Pulmonary embolism
Unrelated
Grade 3 Mental status changes
Unrelated
Source: Table 14.3.1.1.2
Starting from 08 June 2016, use of prophylaxis for diarrhea, nausea and vomiting in the first 
cycle of PF-06647020 was permitted (at the discretion of treating physician) and incidence 
and severity of these adverse events were reduced. 
Two patients (1.9%) experienced Grade 2 and 3 infusion-related reactions at the 2.8 mg/kg 
dose level, starting post infusion in Cycle 1, and lasting 1 and 2 days respectively. The 
infusion-related reactions in both patients were well managed by treatment of antihistamines 
and steroids in following the guidance provided in the protocol, and this adverse event did 
not recur in subsequent cycles in either patient. Guidelines for the management of 
infusion-related reactions and severe hypersensitivity reaction are found in Section 5.4.  
Most commonly (10%) reported drug related AEs in 42 OVCA patients (treated at 
RP2D 2.8 mg/kg) are summarized in Section 1.2.4. Severity of AEs observed in OVCA 
patients were mostly limited to Grade 1-2.  A total of 15 patients (35.7%) experienced a
Grade 3 treatment-related AE, of which most common AEs were neutropenia (10 patients, 
23.8%), and headache, myalgia, vomiting, and hypomagnesaemia (2 patients (4.8%) each).


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Table 6.
Most Frequently Reported (Incidence 10%) Treatment-Related TEAEs in 
OVCA Patients Treated at 2.8 mg/kg PF-06647020 (Any Grade)
MedDRA PT
n (% in total OVCA n=42 patients)
Number of patients with at least 1 TEAE
38 (90.5)
Nausea
19 (45.2)
Alopecia
16 (38.1)
Fatigue
16 (38.1)
Neutropenia
13 (31.0)
Headache
12 (28.6)
Arthralgia
9 (21.4)
Myalgia 
9 (21.4)
Decreased appetite 
8 (19.0)
Vomiting
8 (19.0)
Constipation
6 (14.3)
Anemia
5 (11.9)
Peripheral sensory neuropathy
7 (16.6)
Source: Table 14.3.1.3.11.2
An essentially similar safety profile was observed in 22 patients with NSCLC that received 
PF-06647020 at RP2D 2.8 mg/kg, which is summarized in Table 7.
Table 7.
Most Frequently Reported (Incidence 10%) Treatment-Related TEAEs in 
NSCLC Patients Treated at 2.8 mg/kg PF-06647020 (Any Grade)
MedDRA PT
n (% in total NSCLC n= 22 patients)
Number of patients with at least 1 TEAE
18 (81.8)
Alopecia
9 (40.9)
Fatigue
9 (40.9)
Arthralgia
8 (36.4)
Nausea
8 (36.4)
Diarrhea
5 (22.7)
Headache
5 (22.7)
Vomiting
5 (22.7)
Neutropenia
5 (22.7)
Myalgia
4 (18.2)
Decreased appetite
3 (13.6)
Source: Table 14.3.1.3.11.1
Additional information for this compound may be found in the Single Reference Safety
Document (SRSD), which for this study is the Investigator Brochure.22


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1.2.4.1. Pharmacokinetics (PF-06647020)
Pharmacokinetics of PF-06647020 (ADC, measured as conjugated antibody), hu6M024 mAb 
(total antibody), and PF-06380101 (unconjugated payload) following the first 1-hour infusion 
of PF-06647020 have been characterized in 59 patients treated in the dose escalation and the 
dose expansion phases of the ongoing First-in-Patient (FIP) study, B7661001.  This 
preliminary analysis revealed that the systemic exposure based on area under the 
concentration-time curve during the dosing interval (AUC) and maximum concentration 
(Cmax) values for ADC, total antibody, and unconjugated payload generally increased in a 
dose related manner across the 0.2, 0.5, 1.25, 2.1, 2.8, and 3.7 mg/kg doses.  Apparent 
terminal half-life (t1/2) values for ADC and total antibody tended to increase with doses with 
comparable half-life values among 2.1, 2.8, and 3.7 mg/kg doses, likely related to target 
mediated disposition at lower doses.   
The Cycle 1 PK parameters were comprehensively characterized for the 2.8 mg/kg dose 
level, where data were available from 41 patients. Following single IV infusion of 
PF-06647020 at dose of 2.8 mg/kg, ADC and total antibody peak concentrations (82.6 and 
86.9 g/mL respectively) occurred at or shortly after the end of infusion, followed by a 
multi-phasic decline of concentrations with terminal t1/2 values of approximately 2.7 and
3.3 days for ADC and total antibody, respectively.  Unconjugated payload (PF-06380101) 
concentrations appeared to increase following PF-06647020 infusion and reached a mean 
Cmax of 8.8 ng/mL at 24 h post-dose, and the mean t1/2 was 2.9 days. There were no 
appreciable drug accumulations over repeated doses following Q3W regimen.   
1.2.4.2. Efficacy in Patients treated with PF-06647020 
As of 17 March 2017, total of 112 patients with heavily pre-treated cancers have been treated 
with PF-06647020 on a Q3W regimen at different dose levels in the ongoing Phase I study, 
of which 44 were OVCA patients, 25 were NSCLC patients, and 31 were TNBC patients, 
12 patients had other types of solid tumor.
Of the total 44 OVCA patients who received PF-06647020 treatment, 42 were treated at 
2.8 mg/kg, 1 at 2.1 mg/kg, and 1 at 3.7 mg/kg.  In 38 patients who were considered evaluable 
for ORR assessment, 9 patients achieved objective response (1 CR, and 8 PR) with an ORR 
of 24% (95% CI, 13%, 39%) and 18 patients (47%) had a best response with SD. Median 
PFS was 12.6 weeks (95% CI, 12, 24). Median duration of treatment with PF-06647020 was 
8.1 weeks (range 0.1-45.3 weeks).
Of the total 25 NSCLC patients received PF-06647020 treatment, 22 were treated at 
2.8 mg/kg, 2 at 1.25 mg/kg, 1 at 2.1 mg/kg. In 23 patients who were considered evaluable 
for ORR assessment, 4 patients achieved PR with an ORR of 17% (95% CI, 7%, 37%) and 
9 patients (39%) had a best response with SD. Median PFS was 18.1 weeks (95% CI, 
6, 30.1) and median duration of treatment with PF-06647020 was 9.0 weeks (range 
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Of the total 31 TNBC patients received PF-06647020 treatment, 27 were treated at 
2.8 mg/kg, 2 at 2.1 mg/kg, 2 at 3.7 mg/kg.  In 27 patients who were considered evaluable for 
ORR assessment, 6 achieved PR with an ORR of 22% (95% CI, 11%, 41%).  Eight (30%) 
patients had a best response of SD.  Median PFS was 8.3 weeks (95% CI, 6, 23.6) and a 
median duration of treatment with PF-06647020 was 3.0 weeks (range 0.1-40.3 weeks). 
1.3. Starting Dose Rationale
The selection of the starting dose of PF-06647020 for this FIP study is based on the 
preclinical toxicology results in accordance with the International Conference on 
Harmonization (ICH) S9 Guidance entitled “Nonclinical Evaluation for Anticancer 
Pharmaceuticals”.  Cynomolgus monkey was considered to be the most appropriate species 
for determining the proposed starting dose in patients.  The HNSTD in cynomolgus monkey 
was determined to be 4 mg/kg. The proposed starting dose of 0.2 mg/kg given as an IV 
infusion Q3W represents approximately 1/6th of monkey HNSTD (based on human 
equivalent dose normalized to body surface area).  In addition, given the projected human PK 
parameters based on allometric scaling from cynomolgus monkey PK, the projected human 
Cav for PF-06647020 at the proposed starting dose of 0.2 mg/kg is expected to be 
approximately 1/11th of the observed monkey Cav at HNSTD. 
PK/PD parameters were estimated from mouse xenograft models where at least 3 different 
doses of PF-06647020 were evaluated (Figure 2, TNBC BR13, TNBC BR22). The PK/PD 
relationship between mouse PF-06647020 concentration and measured xenograft tumor size 
data was analyzed based on a cell distribution transduction pharmacodynamic model. 
Human dose prediction was achieved by assuming direct translation of the mouse xenograft 
PD parameters and predicted human PK parameters. Stasis was considered as a criterion for 
minimal efficacy in the clinic compensating for the difference in tumor growth rates between 
xenograft and clinical tumors.  Based on these projections, an efficacious clinical dose of 
1.5 to 1.6 mg/kg of PF-06647020 administered once every 3 weeks is expected to achieve 
concentrations of PF-06647020 sufficient to drive efficacy. 
1.4. PTK7 Immunohistochemistry (IHC) Assay for PTK7 Expression
A PTK7-specific IHC assay was developed using control cancer cell lines with a range of 
PTK7 expression reflective of PTK7 expression in clinical samples.  The PTK7 high, 
moderate, low and negative control cancer cells lines were characterized for PTK7 mRNA 
expression and protein levels using qRT-PCR, nanostring and western blot methodologies.  
Xenografts from the control cell lines were stained with the IHC assay and PTK7 membrane 
expression was assessed.  PTK7 H-scores were highly correlated with PTK7 readouts from 
orthogonal methodologies (qRT-PCR, nanostring and western blot).  Control cell line 
xenografts were subjected to various pre-analytical variables (eg, time to fixation and time of 
fixation) and stained with the PTK7 IHC assay.  The IHC assay was robust to pre-analytic 
variables, enabling the IHC assay to be performed on routinely collected formalin-fixed 
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PTK7 expression as measured by IHC staining was evaluated in 73 whole slide sections of 
formalin-fixed, paraffin-embedded epithelial malignancies of lung, ovary, and breast.  
H-scores were generated based on PTK7 membrane staining of tumor epithelial cells and 
ranged from 0 to 273. Stromal staining was also observed in at least one-third of the cases. 
PTK7 H-scores correlated with PTK7 readouts from orthogonal methodologies (qRT-PCR, 
nanostring and western blot). 
The PTK7 H-scores were ranked lowest to highest and the resulting graph reflects the 
dynamic range of PTK7 expression within an indication.  The ranked IHC values were then 
divided into lowest, middle, and highest statistical tertiles based on total patient number.  The 
middle one-third tertile of H-scores define the moderate PTK7 expressing tumors, whereas 
the tertile with the highest H-score values define the high PTK7 expressing tumors. 
 
 
 
 
 
  A digital H-score is being implemented.
 
 
 
A digital H-score is being implemented.
 
 
 
Figure 3.
PTK7 H-scores in NSCLC, Breast and Ovarian Cancers
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1.5. Triple Negative Breast Cancer, NSCLC and OVCA in Dose Expansion
The selection of the indications in dose expansion was based on the literature reviews, the 
expression of PTK7 in human TNBC, NSCLC and OVCA samples, the efficacy 
demonstrated in preclinical studies, and early signs of efficacy in this study.
1.6. Rationale for Expansion of OVCA Cohort (Protocol Amendment 5)
To further understand PF-06647020 anti-tumor activity in ovarian cancer, the protocol is 
amended to enroll approximately 25 additional patients with OVCA who are 
platinum-resistant or refractory for further evaluating the anti-tumor activity of 
PF-06647020.  This additional enrollment is supported by the following statistical model 
assessment: Based on preliminary early readout of the ongoing Part 2 OVCA study, an 
approximately 27% of ORR is assumed for the available evaluable patients, and an inference 
can be made for the next 24 evaluable patients (including on-going patients) using Bayesian 
probability of achieving a target ORR (in the 50 evaluable patients).  Assuming a uniform 
prior (ie, Beta(1,1)), if 9, 10, 11 and 12 responses are observed in the next 24 evaluable 
patients, then a posterior probability of 65%, 78%, 88% and 94%, respectively, would be 
predicted to achieve ORR 30% in all 50 evaluable OVCA patients.  Analogously, a 66%, 
78%, 87% and 94% predictive probability would be achieved if there are respectively 11, 12, 
13 and 14 responses out of the next 24 evaluable patients when ORR 34% is targeted in all 
50 evaluable OVCA patients.  Note that ORR 34% in 50 evaluable patients implies that the 
lower bound of the 95% confidence interval (CI) of this ORR is >20% which is the null
hypothesis (Ho) in the sample size calculation.  The Bayesian model is specified by a prior 
distribution (Beta function), sampling distribution (binomial function), response predictions 
and probability of exceeding a critical threshold.  The calculation is done using Markov 
Chain Monte-Carlo methods (eg, in OpenBUGS – an open source computing tool for 
Bayesian inference Using Gibbs Sampling).
This expansion study (Protocol Amendment 5) was discontinued and the protocol has been
amended to investigate Q2W PF-06647020 as a single agent and in combination with 
avelumab treatment (Protocol Amendment 7) in patients with OVCA and NSCLC.
1.7. Rationale for DDI Sub-Study
The major cytochrome P450 isoform involved in the metabolism of the unconjugated 
payload (PF-06380101) in humans was determined to be CYP3A4. (See
Section 1.2.2 Nonclinical Pharmacokinetics).  Physiologically-based PK modeling in 
SimCYP, utilizing nonclinical and preliminary clinical data, predicted an average 2- to 
10-fold increase in unconjugated payload AUC with co-administration of ketoconazole, a
potent CYP3A4 inhibitor, at a clinical dose (200 mg twice daily [BID]). Moderate 
CYP3A4 inhibitors, such as fluconazole, are predicted to have less impact on unconjugated 
payload AUC than ketoconazole, with average AUC increase estimated approximately 2-fold 
at clinical doses.  The effect of fluconazole on unconjugated payload exposure cannot be 
precisely predicted at this time due to the lack of certainty surrounding the overall 
contribution of the CYP3A4 pathway to elimination of PF-06380101. A DDI sub-study will 
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unconjugated payload (PF-06380101), when fluconazole is co-administered with ADC 
(PF-06647020). 
The primary aim of the DDI sub-study is to verify the DDI related PK alterations 
(eg, decreased clearance of unconjugated payload) and to enable informed decisions 
regarding inclusion of patients taking concomitant medications, specifically 
CYP3A4 inhibitors. 
See Appendix 7 for details.
Complete information for fluconazole may be found in the SRSD, which for this study is the 
Investigator Brochure (IB).
2. STUDY OBJECTIVES AND ENDPOINTS
2.1. Objectives
2.1.1. Objectives – Dose Escalation (Part 1)
Primary Objectives
•
To assess safety and tolerability at increasing dose levels of PF-06647020
administered intravenously on an every 21-day dosing schedule to patients with 
advanced solid tumors unresponsive to currently available therapies, or for whom no 
standard therapy is available.
•
To determine the MTD and select the RP2D. 
Secondary Objectives
•
To evaluate the overall safety profile.
•
To characterize the single and multiple dose PK of ADC (PF-06647020), total 
antibody (hu6M024 mAb) and unconjugated payload (PF-06380101).
•
To evaluate the immunogenicity as measured by presence of ADA in patients treated 
with PF-06647020.
•
To document any preliminary evidence of anti-tumor activity.
2.1.2. Objectives – Dose Expansion (Part 2)
Primary Objective 
•
To further evaluate safety and tolerability of PF-06647020 at the MTD and to 
establish RP2D in patients with NSCLC, TNBC and OVCA.
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Secondary Objectives
•
To evaluate the overall safety profile at the RP2D.
•
To evaluate preliminary anti-tumor activity of PF-06647020 at the RP2D in patients 
with NSCLC, TNBC and OVCA.
•
To characterize the single and multiple dose PK of ADC (PF-06647020), total 
antibody (hu6M024 mAb) and unconjugated payload (PF-06380101).
•
To evaluate the immunogenicity as measured by presence of ADA in patients treated 
with PF-06647020.
•
To evaluate the effect of the co-administration of fluconazole on the PK of 
unconjugated payload (PF-06380101), ADC (PF-00647020) and total antibody 
(hu6M024 mAb) following administration of ADC (PF-06647020).
•
To assess the effects of fluconazole on the safety and tolerability of a single dose of 
PF-06647020.
 
 
 
 
 
2.2. Endpoints
2.2.1. Endpoints – Part 1
Primary Endpoint (Part 1)
•
First cycle DLTs in order to determine the MTD and RP2D of 
PF-06647020 administered by IV infusion in a 21-day dosing cycle.
Secondary Endpoints (Part 1)
•
Adverse events as characterized by type, frequency, severity (as graded by 
NCI-CTCAE v.4.03), timing, seriousness and relationship to study treatment.
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•
Laboratory abnormalities as characterized by type, frequency, severity 
(as graded by NCI CTCAE v. 4.03) and timing.
•
Single and multi-dose PK parameters of multiple analytes [ADC (PF-06647020), total 
antibody (hu6M024 mAb) and unconjugated payload (PF-06380101)].
•
Incidence of anti-PF-066407020 antibodies. 
•
Preliminary evidence of anti-tumor activity based on RR, as assessed using 
RECIST version 1.1. 
2.2.2. Endpoints – Part 2
Primary Endpoints (Part 2)
•
Adverse events as characterized by type, frequency, severity (as graded by NCI 
CTCAE v.4.03), timing, seriousness and relationship to study treatment.
•
Laboratory abnormalities as characterized by type, frequency, severity 
(as graded by NCI CTCAE v. 4.03) and timing.
Secondary Endpoints (Part 2)
•
OR, DoR, DCR, TTP, and PFS, as determined by Investigator [As assessed by 
RECIST version 1.1].
•
Single and multi-dose PK parameters of multiple analytes [ADC (PF-06647020), total 
antibody (hu6M024 mAb) and unconjugated payload (PF-06380101)].
•
Incidence of anti-PF-066407020 antibodies. 
•
The PK parameters of ADC (PF-06647020), total antibody (hu6M024 mAb) and 
unconjugated payload (PF-06380101) following ADC (PF-06647020) administration 
alone and when co-administered with fluconazole.
 
 
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Study OBJECTIVES AND ENDPOINTS for the Q2W regimen expansion can be found in
Appendix 8.
3. STUDY DESIGN
3.1. Study Overview
This is a Phase 1, open label, multi-center, non-randomized, multiple dose, safety, 
pharmacokinetic and pharmacogenomic study, initially designed to evaluate single agent 
PF-06647020 in sequential cohorts of adult patients with advanced solid tumors unresponsive 
to currently available therapies or for whom no standard therapy is available.  Successive 
cohorts of patients received doses of PF-06647020 intravenously Q3W starting at a dose of 
0.2 mg/kg.
This clinical study will include two parts.  Part 1 will estimate the MTD/RP2D in dose 
escalation cohorts in patients with advanced solid tumors unresponsive to currently available 
therapies or for whom no standard therapy is available.  Part 2 will include approximately 
87 patients enrolled at a RP2D selected by the Sponsor and Investigators from Part 1, to 
explore benefit from treatment and to better define the safety profile, as well as the RP2D.  
This expansion cohort will include approximately 22 patients with metastatic or recurrent 
TNBC, 45 OVCA patients and 20 patients with advanced NSCLC. 
 
 
 
 
 
 
A DDI sub-study for evaluating the effect of multiple-dose fluconazole on the PK of 
unconjugated payload (PF-06380101) is currently ongoing.
The DDI sub-study is an open-label, 2-period, fixed sequence design in up to 10 patients to 
determine the effect of multiple-dose fluconazole, a model moderate CYP3A4 inhibitor, on 
the PK of ADC (PF-06647020), total antibody (hu6M024 mAb) and unconjugated payload 
(PF-06380101), when fluconazole is co-administered with PF-06647020. The sub-study will 
be in a separate cohort from the studies for TNBC, NSCLC and OVCA, and study design and 
procedure details can be found in Appendix 7.
Approximately 190 patients enrolled from 15-20 sites will participate in this study (including 
the Q2W Regimen Expansion).  The actual number of patients enrolled will depend upon 
tolerability of PF-06647020 and the number of dose levels required to identify the 
MTD/RP2D. 
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Patients will participate in the study for approximately 6 months or until disease progression, 
(PD) as per RECIST 1.1 (or irRECIST in Cohort 3 of the Q2W regimen expansion), patient
withdrawal of consent or unacceptable toxicity occurs, patient loss to follow up, or the study 
is terminated by the Sponsor, whichever comes first.  This includes a 4 week screening 
period, a 4 month treatment period and a 4 week post dose follow-up period.  A follow-up 
visit within 4 weeks after the last dose of study drug for AE and SAE collection will be 
conducted.  The time on study can vary depending on the observed toxicity and potential 
benefit an individual patient derives.  The study is expected to be completed in 
approximately 36 months. 
This study is being expanded, in this Amendment 7, for safety, PK and efficacy evaluation of 
the Q2W dosing schedule for PF-06647020 as a single agent treatment or in combination 
with avelumab in patients with platinum resistant or refractory OVCA and recurrent
advanced NSCLC. The Q2W regimen expansion is included as a sub-study to this protocol;
the design and procedure details can be found in Appendix 8.
3.2. Dose Escalation Phase (Part 1)
A modified toxicity probability interval (mTPI) method, targeting a DLT rate of 25% and an 
acceptable DLT interval (20%-30%)8 will be utilized in Part 1 (see Table 8). 


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Table 8.
Dose Escalation Table  
Number of patients treated in current dose
DLT
n=2
n=3
n=4
n=5
n=6
n=7
n=8
n=9
0
E
E
E
E
E
E
E
E
1
na
S
S
S
E
E
E
E
2
U
D
D
S
S
S
S
S
3
na
U
U
D
D
S
S
S
4
na
na
U
U
U
D
D
D
5
na
na
na
U
U
U
U
U
6
na
na
na
na
U
U
U
U
7
na
na
na
na
na
U
U
U
8
na
na
na
na
na
na
U
U
9
na
na
na
na
na
na
na
U
D: De-escalate the dose; E: Escalate the dose; S: Stay at the dose; U:Unacceptable toxicity, na: Not 
applicable
The target size of each cohort will be 3 patients.  However, patients may be enrolled in 
cohorts of 2-4, starting with 0.2 mg/kg for the first cohort.  In cohorts with 2 patients 
enrolled, an additional patient may be enrolled for dose escalation assessment if one of the 
two patients has a DLT.  Subsequent dose levels may include a maximum 250% escalation 
until either the dose reaches 1.25 mg/kg, or a patient experiences a DLT.  Starting from 
1.25 mg/kg, dose escalation in subsequent cohorts will follow a modified Fibonacci scheme 
with maximum dose increases of 68%, 34%, 33%, 33%, and 33%, respectively.  If a high 
DLT rate is observed at the starting dose, a lower dose (eg, 0.1 mg/kg) will be considered.  
The study may be stopped if the drug is deemed not tolerable at the lowest dose. Table 9
illustrates the potential dose levels in the dose escalation Part 1 study.
Table 9.
Table of Potential Dose Levels 
Dose Level
Dose
(mg/kg)
-1
0.10
1 (starting dose)
0.20
2
0.50
3
1.25
4
2.10
5
2.80
6
3.70
7
4.90
*Modified Fibonacci^ scheme starts from dose level 3
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. Doses higher than 
1.25 mg/kg will be escalated no greater than 68%.  In the event dose de-escalation is 
required, an intermediate dose between the dose that requires de-escalation and the dose 
immediately prior will be considered. In any event, no patients should be treated at the dose 
level that has been de-escalated or higher for the remainder of the study.


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The algorithm will stop if any of the following criteria is met:
1. The maximum sample size has been achieved (approximately 40 patients total).
2. At least 9 patients have been accumulated on a dose that is predicted to be the MTD.
3. All doses explored appear to be overly toxic and the MTD cannot be determined.
Although dose levels are capped at 4.90 mg/kg in the table illustrated (Table 9), the mTPI 
will continue to operate subject to the constraints detailed above while allowing for doses 
higher than specified.  Doses beyond 4.90 mg/kg may be allowed in 30% increments if 
necessary. 
All clinically relevant AEs and SAEs will be reviewed by the sponsor and investigators to 
determine if the dose allocation schedule requires modification. 
Patients will continue with study treatment every 21 days 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. 
In the first cohort of the study there will be a minimum of 48 hours separation between 
dosing of each patient.
The Q2W regimen expansion sub-study contains a dose escalation portion (Part 1) using the 
mTPI method and dose expansion portion (Part 2); details of the sub-study are included in 
Appendix 8.
3.3. DLT Definition
Severity of adverse events will be graded according to CTCAE version 4.03. For the purpose 
of dose escalation (Part 1), any of the following adverse events occurring in the first cycle of 
treatment (within 21 days of first dose or until patient receives 2nd infusion if there are 
treatment delays) will be classified as DLTs, unless there is a clear alternative explanation 
(eg, related to underlying disease/progression):

Hematologic:

Grade 4 neutropenia lasting >7 days;

Febrile neutropenia (defined as neutropenia Grade 3 and a single body 
temperature >38.3°C or a sustained temperature of 38°C for more than one 
hour;

Grade 3 neutropenic infection; 


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
Grade 4 anemia;

Grade 3 thrombocytopenia with clinically significant bleeding;

Grade 4 thrombocytopenia:

any <10,000;

10,000-25,000 for >3 days.

Hepatic:

Grade 3 serum bilirubin, hepatic transaminase (alanine aminotransferase [ALT]
or aspartate aminotransferase [AST]) or alkaline phosphatase. For patients with 
Grade 2 hepatic transaminase or alkaline phosphatase levels at baseline as a result 
of liver metastasis or bone metastasis, a hepatic transaminase or alkaline 
phosphatase level >10 times the upper limit of normal (ULN) will be considered 
as a DLT. 

ALT or AST 3.0 x ULN concurrent with elevation in bilirubin 2.0 x ULN.

Non-hematologic, non-hepatic:

Grade 3 toxicities that are considered non-hematologic, non-hepatic major organ 
toxicity (excluding alopecia of any grade, Grade 3 diarrhea that responds to 
therapy, and Grade 3 nausea and vomiting in the absence of premedication that 
responds to therapy). 

Delay by more than 2 weeks in receiving the next scheduled cycle due to 
persisting toxicities attributable to PF-06647020.
In addition, clinically important or persistent toxicities that are not included in the above 
criteria may be considered a DLT following review by Pfizer and the investigators.  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 Pfizer. 
In principle, a patient needs to be on study for at least 21 days to be evaluable for DLT 
observation, and may be replaced if they terminate study participation earlier than 21 days.  
However, in circumstances of an event not related to study drug (eg, traffic accident, clear 
disease progression) that leads to study termination close to/before 21 days, the patient might 
be deemed evaluable if the investigators and sponsor agree.
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3.4. 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%]. 
The MTD will be the highest dose in the EI.
3.5. Dose Expansion Phase (Part 2)
The expansion cohorts will include approximately 22 patients with metastatic or recurrent 
TNBC, 45 OVCA patients and 20 patients with advanced NSCLC.  
 
 
 
 
Additional safety information gathered in Part 2 may be used to modify the dose 
recommended for future Phase 2 trials.
3.6. Recommended Phase 2 Dose (RP2D) Definition
The RP2D is the dose chosen for further study based on Phase 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.
4. PATIENT SELECTION
This study can fulfill its objectives only if appropriate patients are enrolled.  The following 
eligibility criteria are designed to select patients for whom protocol treatment is considered 
appropriate.  All relevant medical and non-medical conditions should be taken into 
consideration when deciding whether this protocol is suitable for a particular patient.
PATIENT SELECTION details for the Q2W regimen expansion are included in Appendix 8. 
4.1. Inclusion Criteria
Patient eligibility should be reviewed and documented by an appropriate member of the 
investigator’s study team before patients are included in the study.
Patients must meet all of the following inclusion criteria to be eligible for enrollment into the 
study:
1. For the dose escalation phase (Part 1): Histological or cytological diagnosis of solid 
tumor that is advanced/metastatic and resistant to standard therapy or for which no 
standard therapy is available.
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2. For the dose expansion phase (Part 2): Histological or cytological diagnosis of the 
following:
a.
 
  The TNBC is characterized by:
•
≤1% of tumor cell nuclei immunoreactive for ER or PR;
and
•
IHC ≤2+ for HER2 or a fluorescence in situ hybridization ratio of 
<2.2 (HER2 to CEP17) or average HER2 gene copy number fewer than 
6 signals per nucleus without an internal control.
b.
  
Patients with adenocarcinoma subtype NSCLC should be tested for ALK 
alterations and EGFR mutations and have exhausted all FDA-approved available 
targeted therapies. 
c.
Advanced epithelial ovarian cancer, primary peritoneal or primary fallopian tube 
cancer (OVCA).  All patients must have progressed while receiving or within 
6 months after completion of at least 4 cycles of the most recently administered 
platinum-containing therapy regimen (single agent or combination).  Patient’s 
prior line of therapy could be up to a maximum of three chemotherapy regimens 
with approved agents (single or combination), as long as the following criteria are 
met: 
1. Requirements for first line therapy: Patients must have received first-line 
treatment with a taxane/platinum based combination chemotherapy.  Patients 
must have experienced disease progression during administration of or within 
6 months after completing at least 4 cycles of the first line therapy. A third 
therapeutic agent is permitted if it is part of the initial first line treatment.  A 
neo-adjuvant and an adjuvant chemotherapy constituting of a platinum and a 
taxane (cisplatin or carboplatin and docetaxel or paclitaxel) should be 
considered as one line of treatment providing that the treatment free interval is 
less than four months (calculated from the last administration of the 
neo-adjuvant regimen to the first administration of the adjuvant regimen).
2. Requirements for patients who received two prior line of therapy: The first 
line regimen must be as described in Section 2.1.1.  The second line regimen 
must consist of either platinum salt, gemcitabine, docetaxel, paclitaxel, 
cyclophosphamide, liposomal doxorubicin, or topotecan, administered as a 
single agent or in combination therapy.
3. Requirements for patients who received three prior regimens: the first and 
second line of prior regimens must be as described in Section 2.1.2.  The third 
line regimen must consist of a platinum salt as a single agent or in 
combination with gemcitabine, docetaxel, paclitaxel, cyclophosphamide, 
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liposomal doxorubicin, or topotecan.  Patients must have progressed within 
6 months of receiving at least 4 cycles of third line therapy or should have 
experienced documented disease progression, or toxicity requiring cessation 
of treatment.
Patients who received consolidation/maintenance therapy with approved agent 
after completion of the platinum-based chemotherapy (ie, additional cycles of a 
taxane) are permitted to enroll in the study proving they experienced documented 
disease progression within 6 months from last administration of platinum-based 
chemotherapy.
 
3. For the dose escalation phase (Part 1): Patients may have measurable or 
non-measurable disease.
4. For the dose expansion phase (Part 2): TNBC and NSCLC patients must have at least 
one measurable lesion as defined by RECIST version 1.1.  OVCA patients must 
either be measurable according to RECIST version 1.1 or assessable according to the 
Gynecological Cancer Intergroup (GCIG, 2011)18 CA-125 criteria and require 
chemotherapy treatment. 
5.
 
 
 
 
 
 
 
 
 
 
 
6. Adults age ≥18 years. 
7. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1.
8. Adequate bone marrow function, including all of the following:
a.
Absolute Neutrophil Count (ANC) ≥1,500/mm3 or ≥1.5 x 109/L;
b. Platelets ≥100,000/mm3 or ≥100 x 109/L;
c.
Hemoglobin ≥9 g/dL.
9. Adequate renal function, including all of the following:
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a.
Serum creatinine 1.5 x upper limit of normal (ULN) or estimated creatinine 
clearance 60 ml/min as calculated using the method standard for the institution.
10. Adequate liver function, including all of the following:
a.
Total serum bilirubin 1.5 x ULN unless the patient has documented Gilbert 
syndrome;
b. Aspartate and alanine transaminase (AST & ALT) 3.0 x ULN; 5.0 x ULN if 
there is liver metastasis;
c.
Alkaline phosphatase 2.5 x ULN; (5 x ULN in case of bone metastasis and/or 
hepatic metastasis). 
11. Resolved acute effects of any prior or ongoing anti-cancer therapy to baseline severity 
or CTCAE Grade 1 except for AEs not constituting a safety risk by investigator 
judgment. 
12. Negative serum/urine pregnancy test (for females of childbearing potential) at 
screening and within 72 hours of starting treatment.
13. Male and female patients of childbearing potential and at risk for pregnancy must 
agree to use two highly effective methods of contraception throughout the study and 
for at least 30 days after the last dose of assigned treatment. 
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: 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 females that 
are <60 years old. 
14. Evidence of a personally signed and dated informed consent document indicating that 
the patient has been informed of all pertinent aspects of the study.
15. Patients who are willing and able to comply with the study scheduled visits, treatment 
plans, laboratory tests and other procedures. 
16. Life expectancy of at least three months.
DDI Sub-Study: See Appendix 7 for additional inclusion criteria.


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4.2. Exclusion Criteria
Patients presenting with any of the following will not be included in the study:
1. Patients with known symptomatic brain metastases requiring steroids.  Patients with 
previously diagnosed brain metastases are eligible if they have completed their 
treatment and have recovered from the acute effects of radiation therapy or surgery 
prior to the start of study medication, have discontinued corticosteroid treatment for 
these metastases for at least 4 weeks and are neurologically stable.
2. Major surgery, radiation therapy (other than palliative radiotherapy to lesions that will 
not be followed for tumor assessment on this study ie, non-target lesions) or systemic 
anti-cancer therapy within 3 weeks or 5 half-lives (whichever is shorter) of starting 
study treatment (6 weeks for mitomycin C or nitrosoureas) or hormonal, biological or 
investigational agents within 2 weeks [or within 5 times the half-life of the agent
(whichever is shorter)] of starting study treatment.  If the immediate prior regimen 
included only weekly chemotherapy, then a 2 week washout period is acceptable.
3. Previous high dose chemotherapy requiring stem cell rescue.
4. Presence of Grade 2 peripheral neuropathy.
5. OVCA patients with any of the following:
a.
Non-epithelial, including malignant mixed Müllerian tumors. 
b. Ovarian tumors with low malignant potential (ie, borderline tumors). 
c.
Previous treatment with > three (3) anti-cancer regimens.
d. Any prior radiotherapy to the pelvis or abdomen.
e.
Patients with CA-125-only disease.
f.
Previous exposure to murine CA-125 antibody (only applicable to those patients 
with non-measurable disease by RECIST version 1.1) (Appendix 2).
g. Unresolved bowel obstruction, including sub-occlusive disease, related to the 
underlying disease and history of abdominal fistula, gastrointestinal perforation or 
intra-abdominal abscess. 
6. Prior treatment with a compound of the same mechanism.
7. Currently receiving active treatment in another clinical study.
8. Patients currently on or anticipated to be put on either strong CYP3A inhibitors or 
inducers (defined in US Food and Drug Administration (FDA) guidance “Drug 
interaction studies - study design, data analysis, implications for dosing and labeling 


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recommendations” and summarized in Appendix 6).  Patients may undergo a washout 
period of 4 to 5 times the half-life of the inducer or inhibitor prior to enrollment in the 
study.
9. Active and clinically significant bacterial, fungal or viral infection including known 
hepatitis B (HBV), hepatitis C (HCV), human immunodeficiency virus (HIV) or 
acquired immunodeficiency syndrome (AIDS)-related illness.
10. Any of the following in the previous 12 months: myocardial infarction, 
severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic 
congestive heart failure, cerebrovascular accident, transient ischemic attack or 
symptomatic pulmonary embolism.
11. Known or suspected hypersensitivity to recombinant human or murine proteins.
12. Any ongoing cardiac dysrhythmias of NCI CTCAE Grade 2, any grade of atrial 
fibrillation, or QTcF interval >470 msec, except for documented Right Bundle 
Branch Block, at screening. 
13. Other severe acute or chronic medical or psychiatric 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. 
14. 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 trial.
15. Pregnant female patients; breastfeeding female patients; male and female patients of 
childbearing potential who are unwilling or unable to use two (2) highly effective 
methods of contraception as outlined in this protocol for the duration of the study and 
for at least 30 days after last dose of investigational product. 
DDI Sub-Study: See Appendix 7 for additional exclusion criteria.
4.3. Lifestyle Guidelines 
In this study, male patients who are able to father children and female patients who are of
childbearing potential receive PF-06647020, a compound for which a teratogenic risk is 
currently unknown.  Those who, in the opinion of the investigator, are sexually active and at 
risk for pregnancy must agree to use two (2) methods of highly effective contraception 
throughout the study and continue to do so for at least 30 days after the last dose.  The 
investigator or his/her designee, in consultation with the patient, will select two appropriate 
methods of contraception for the individual patient from the list of permitted contraception 
methods (see below) and instruct the patient in their consistent and correct use.  Patients need 


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to affirm that they meet the criteria for correct use of 2 of the selected methods of 
contraception.  The investigator or his or her designee will discuss with the patient the need 
to use 2 highly effective contraception methods 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 one or 
both selected contraception methods are 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 are 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.
UK only: Per Medicines and Healthcare products Regulatory Agency (MHRA), a 
condom with or without spermicide is not considered a highly effective method of 
contraception in the UK. Other highly effective methods of contraception described 
in this section should be used.
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).
Female patients of non-childbearing potential must meet at least one of the following 
criteria:

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; status may be confirmed by having a serum 
follicle-stimulating hormone (FSH) level confirming the post-menopausal state.


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All other female patients (including females with tubal ligations) will be considered 
to be of childbearing potential.
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 at least 28 days after the last 
dose.
Applicable to Appendix 8, UK only: All sexually active male patients must agree to prevent 
potential transfer of and exposure to drug through semen to their partners by using 2 highly 
effective methods of contraception as described in this section, beginning with the first dose 
of investigational product and continuing for at least 120 days after the last dose of 
investigational product (150 days if the male patient is participating in the combination 
cohort with avelumab).
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 Manual.
To facilitate access to appropriately qualified medical personnel on study-related medical 
questions or problems, patients are provided with a contact card. The contact card contains, 
at a minimum, protocol and investigational compound identifiers, patient study numbers, 
contact information for the investigational site, and contact details for a help desk in the 
event that the investigational site staff cannot be reached to provide advice on a medical 
question or problem originating from another healthcare professional not involved in the 
patient’s participation in the study. The help desk number can also be used by investigational 
staff if they are seeking advice on medical questions or problems; however, it should only be 
used in the event that the established communication pathways between the investigational 
site and the study team are not available. It is therefore intended to augment, but not replace, 
the established communication pathways between the investigational site and the study team 
for advice on medical questions or problems that may arise during the study. The help desk 
number is not intended for use by the patient directly, and if a patient calls that number, he or 
she will be directed back to the investigational site.
5. STUDY TREATMENTS
5.1. Allocation to Treatment
Eligible patients will be enrolled to receive PF-06647020 in an open-labeled, unblinded 
manner.  Patients will be successively assigned to the next available treatment slot at a dose 
level decided on after the previous cohort’s safety evaluation and ongoing observations of 
earlier enrolled patients. 
Patient number and dose level allocation will be performed by the sponsor after patients have 
given their written informed consent and have completed the necessary baseline assessments. 
The site staff will email 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 


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CRF pages and other study-related documentation or correspondence referencing that patient 
and email to the site.
No patient shall receive study drug until the investigator or designee has received the 
following information in writing from the sponsor:

confirmation of the patient’s enrollment;

specification of the dose level for that patient; and

permission to proceed with dosing the patient.
The sponsor or designee will notify the other sites of the inclusion of a new patient, and will 
inform study sites about the next possible enrollment date.
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 Investigational 
Product 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. Drug Supplies
PF-06647020 will be supplied for the study by Pfizer. 
Study centers will receive a supply of clinical trial material upon site activation with 
instructions on how to confirm drug receipt.  Resupplies will be made during the course of 
the study based on need.  The details on drug supply will be provided in the Investigational 
Product Manual. The study monitor should be contacted for any issues related to drug 
supplies.
DDI Sub-Study: Commercially-available fluconazole tablets will be provided by the site. 
See Appendix 7 for details.
5.3.1. Dosage Form and Packaging
PF-06647020 for injection, 60 mg extractable per vial, is presented as a sterile lyophilized 
product, white to off white cake, and packaged in a 6 mL glass vial.  Each vial of 
PF-06647020 for injection is reconstituted with water for injection (WFI).  The vial is 
designed for single use.  The packages will be properly labeled according to local regulatory 
requirements.


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Fluconazole Tablets United States Pharmacopeia (USP), for oral administration contains
50, 100, 150, or 200 mg of fluconazole, USP. 
5.3.2. Preparation and Dispensing
See the Investigational Product Manual for instructions in how to prepare the investigational 
product for administration.  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.
5.4. Administration
PF-06647020 will be administered on Day 1 of each 21-day cycle per the Investigational 
Product Manual as an IV infusion over approximately 60 minutes on an outpatient basis. 
Details for preparation and administration of the PF-06647020 infusion are provided in the 
current PF-06647020 Investigational Product Manual. All patients should be weighed within 
72 hours prior to dosing for every cycle to ensure they did not experience either a weight loss 
or gain >10% from the prior weight used to calculate the amount of PF-06647020 required 
for dose preparation. The decision to recalculate PF-06647020 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 
initial dose, the amount of PF-06647020 required for preparation and administration for the 
current cycle must be recalculated using this most recent weight obtained.
A cycle is defined as the time from Day 1 dose to the next Day 1 dose.  If there are no 
treatment delays, a cycle will be 21 days.  Each patient may receive PF-06647020 until 
disease progression, unacceptable toxicity, withdrawal of consent, or study termination. 
In the event of infusion related reactions, Investigators should institute treatment measures 
according to best medical and nursing practice.  The monitoring and treatment guidelines are 
provided in Appendix 5.  In the case of infusion related reactions, characterized by fever and 
chills, and less commonly hypotension, the sponsor should be notified and pre-treatment
medication should be administered prior to subsequent infusions (in the case that the patient 
is able to continue on treatment as per Appendix 5).  The decision to incorporate 
pre-medication in all patients will be made following discussions between the sponsor and 
the investigators.  Patients should be pre-treated with acetaminophen and diphenhydramine 
(or other antihistamine) approximately 0.5 to 2 hours before each 
PF-06647020 administration.  The pre-treatment medications will not be supplied by Pfizer. 
Suggested starting doses are 650 to 1000 mg acetaminophen and 50 mg diphenhydramine (or 
equivalent of other antihistamine) IV or oral.  Two (2) additional doses of acetaminophen 
may be administered approximately every 4 hours after the initial pre-treatment or as needed.


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Details of PF-06647020 Administration in the Q2W regimen expansion are included in 
Appendix 8.
5.4.1. Recommended Dose Modifications
Every effort should be made to administer study treatment on the planned dose and schedule.
In the event of significant toxicity dosing may be delayed and/or reduced as described below.  
In the event of multiple toxicities, dose modification should be based on the worst toxicity 
observed.  Patients are to be instructed to notify investigators at the first occurrence of any 
adverse symptom.
Dose modifications may occur in three ways:

Within a cycle: dosing interruption until adequate recovery and dose reduction, if 
required, during a given treatment cycle; 

Between cycles: next cycle administration may be delayed due to persisting toxicity 
when a new cycle is due to start;

In the next cycle: dose reduction may be required in a subsequent cycle based on 
toxicity experienced in the previous cycle. 
5.4.2. Dose Interruptions/Delays
Patients experiencing Grade 3 or 4 potentially treatment related toxicity or intolerable 
Grade 2 toxicity despite supportive care should have their treatment interrupted/delayed.  
Appropriate follow up assessments should be done until adequate recovery occurs as 
assessed by the investigator. 
If a treatment interruption continues beyond Day 21 of the current cycle, then the day when 
treatment is restarted will be counted as Day 1 of the next cycle.  Re-treatment following 
treatment interruption for treatment related toxicity or at the start of any new cycle may not 
occur until all of the following parameters have been met:

ANC 1,000/mm3;

Platelets count 75,000/mm3;

Non-hematologic toxicities have returned to baseline or Grade 1 severity (or, at the 
investigator discretion, Grade 2 if not considered a safety risk for the patient).
If these conditions are not met, treatment must be delayed by 1 week.  If, after a 1-week 
delay, all toxicities have recovered within the limits described above treatment with 
PF-06647020 can be resumed.  Please refer to section Dose Reductions for adverse events 
requiring dose reduction at the time of treatment resumption. 


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Initiation of the next cycle can only be delayed by a maximum of 2 weeks.  Therefore, if 
persisting toxicity does not allow PF-06647020 treatment resumption within 35 days of 
Day 1 of previous cycle, this will result in discontinuation of the patient from treatment 
unless discussed and agreed with the Sponsor.
5.4.3. Dose Reductions
Following dose interruption or cycle delay due to toxicity, PF-06647020 may need to be 
reduced when treatment is resumed.
No specific dose adjustments are recommended for Grade 1/2 treatment-related toxicity.  
However, investigators should always manage their patients according to their medical 
judgment based on the particular clinical circumstances.
Patients experiencing recurrent and intolerable Grade 2 toxicity may resume dosing at the 
next lower dose level once recovery to Grade 1 or baseline is achieved.
Dose reduction of PF-06647020 by 1 and, if needed, 2 dose levels will be allowed depending 
on the type and severity of toxicity encountered.  Patients enrolled in the first cohort should 
be discontinued from the study if more than 1 dose reduction is required. Patients enrolled in 
subsequent cohorts should be discontinued from the study if more than 2 dose reductions are 
required, unless otherwise agreed between the investigator and the sponsor.  All dose 
modifications/adjustments must be clearly documented in the patient's source notes and CRF. 
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.
For patients experiencing an adverse event related to PF-06647020 that fails to recover to 
CTCAE Grade 1 (or within 1 grade of starting values for pre-existing laboratory 
abnormalities) leading to treatment delay of >2 weeks should be discontinued unless 
discussed with the Sponsor.
Recommended dose reductions are illustrated in Table 10.
Patients experiencing a DLT may resume dosing at the next lower dose level (if applicable) 
once adequate recovery is achieved. 


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Table 10.
Dose Modifications for Toxicity Considered Possibly Drug-Related
Toxicity
Action
Grade 3 or 4 nonhematologic 
toxicity (including persistent 
nausea, vomiting, diarrhea despite 
optimal medical therapy)

Hold PF-06647020 infusion until recovery to Grade 0-1 or baseline 
and reduce by 1 dose level.

Discontinue PF-06647020 if dose delay is more than 2 weeks.

If toxicity reoccurs despite reduction, patient may be dose reduced 
again by another dose level upon recovery to grade 0-1 or baseline 
unless the patient is in the first dose group, then only 1 dose 
reduction is allowed. 

Prompt palliative measures are strongly encouraged 
(eg, anti-emetics). 
Grade 4 nonhematologic toxicity

Patients who experience Grade 4 non hematologic toxicities despite 
intervention should be discontinued from treatment.
Grade 3 hepatic toxicity 
(including serum bilirubin, ALT, 
AST, alkaline phosphatase)

Hold PF-06647020 infusion until recovery to Grade 0-1 or baseline 
and reduce by 1 dose level.

Discontinue PF-06647020 if dose delay is more than 2 weeks.

If toxicity reoccurs despite reduction, patient may be dose reduced 
again by another dose level upon recovery to grade 0-1 or baseline 
unless the patient is in the first dose group, then only 1 dose 
reduction is allowed.
ALT or AST 3.0 x ULN 
concurrent with elevation in 
bilirubin 2.0 x ULN

Discontinue treatment
Hematologic toxicities

Grade 4 neutropenia, ie, ANC 
500/mm3
(0.5 x 109/L) for more than 
7 days. 

Febrile neutropenia, ie, fever 
with a single temp >38.3C or 
sustained temp 38C for more 
than 1 hour with ANC 
<1000/mm3. 

Grade 4 Anemia

Grade 3 Thrombocytopenia 
with bleeding. 

Grade 4 Thrombocytopenia, 
ie, PLTS 25,000 mm3
(25.0 x 109/L).

Hold PF-06647020 until recovery of ANC to 1.0 x 109/L 
(1,000 cells/mm3) and platelets 75 x 109/L (75,000 platelets/mm3).

Reduce PF-06647020 by 1 dose level.

If toxicity reoccurs despite dose reduction, patient may either be 
held until recovery and continuation at same dose, or undergo 
further dose reduction by another dose level unless the patient is in 
the first dose group, then only 1 dose reduction is allowed.
Other grade 4 hematologic toxicity 

Hold PF-06647020 until recovery to Grade 0-1 or baseline and 
reduce PF-06647020 dose by 1 dose level.

If toxicity reoccurs despite dose reduction, patient may either be 
held until recovery and continuation at same dose, or undergo 
further dose reduction by another dose level unless the patient is in 
the first dose group, then only 1 dose reduction is allowed.
No recovery of toxicities within 
2 weeks of scheduled 
PF-06647020 infusion

Discontinue treatment


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5.5. Drug Storage
The investigator, or an approved representative (eg, pharmacist) will ensure that all 
investigational product is stored in a secured area with controlled access under recommended
storage conditions and in accordance with applicable regulatory requirements.
Investigational product should be stored in its original container and in accordance with the 
drug label.  See the Investigational Product Manual for storage conditions of the product.
Storage conditions stated in the SRSD (ie, Investigator Brochure) will be superseded by the 
storage conditions stated in the labeling.
Site systems must be capable of measuring and documenting (for example, via a log), at a 
minimum, daily minimum and maximum temperatures for all site storage locations (as 
applicable, including frozen, refrigerated and/or room temperature products).  This should be 
captured from the time of investigational product receipt throughout study.  Even for 
continuous monitoring systems, a log or site procedure which ensures active daily evaluation 
for excursions should be 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 labeled storage 
conditions, as soon as possible.  Deviations from the storage requirements, including any 
actions taken, must be documented and reported to the sponsor.
Once an excursion is identified, the investigational product must be quarantined and not used 
until the sponsor provides documentation of permission to use the investigational product.  It 
will not be considered a protocol deviation if Pfizer approves the use of the investigational 
product after the temperature excursion.  Use of the investigational product prior to Pfizer
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 products are briefly out of the temperature range described in the labeling are not 
considered excursions. 
5.6. Drug Accountability
The investigator site must maintain adequate records documenting the receipt, use, loss, or 
other disposition of the investigational product supplies.  All investigational products will be 
accounted for using a drug accountability form/record. 
5.6.1. 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 investigator site, the 
investigator must ensure that the materials are destroyed in compliance with applicable 


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environmental regulations, institutional policy, and any special instructions provided by 
Pfizer, and all destruction must be adequately documented.
5.7. 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 including supportive care drugs (eg, anti-emetic treatment and 
prophylaxis), drugs used to treat adverse events or chronic diseases, blood products, as well 
as non-drug interventions (eg, transfusions, analgesic use or paracentesis) received by 
patients within 28 days (4 weeks) prior to first dose of study treatment until the end of study 
visit will be recorded on the CRF.  This will include the name of the procedure or 
medication, route and duration of treatment.
Based on the anticipated low systemic concentrations of released Aur0101, PF-06647020 is 
considered to be of low risk to impact the PK of compounds primarily metabolized by CYP 
enzymes. As Aur0101 is a P-gp substrate and is primarily metabolized by CYP3A4, there 
may be a potential change in Aur0101 PK exposure when PF-06647020 is co-administered 
with potent CYP3A/P-gp inhibitors and/or inducers. Therefore, co-administration of 
PF-06647020 and potent CYP3A/P-gp inhibitors and/or inducers, as listed in Appendix 6, is 
not recommended. Selection of an alternate concomitant medication with no or minimal 
enzyme inhibition and/or induction potential is recommended. Any questions regarding 
administration of concomitant medications should be directed to the sponsor.
During the study, co-administration of potent CYP3A inducers and strong CYP3A inhibitors 
(see Appendix 6) with PF-06647020 is not permitted.  This restriction is included to 
minimize the potential influence of a pharmacokinetic drug interaction on the determination 
of the maximum tolerated dose.  Patients may undergo a washout period of 4 to 5 times the 
half-life of the inducer or inhibitor prior to screening and enrollment in the study.
DDI Sub-Study: See Appendix 7 for further details on concomitant medications.
Guidance for concomitant treatment in the Q2W regimen expansion is included in 
Appendix 8.
5.7.1. Other Anti-tumor/Anti-cancer or Experimental Drugs
No additional anti-tumor treatment including chemotherapy, hormonal therapy, radiotherapy, 
or experimental anticancer medications will be permitted while patients are receiving study 
therapy.  Additionally, the concurrent use of select vitamins or herbal supplements is not 
permitted.
Palliative radiotherapy on study is permitted for the treatment of painful bony lesions 
providing the lesions were known at the time of study entry and the investigator clearly 
indicates that the need for palliative radiotherapy is not indicative of disease progression. 


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5.7.2. 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. 
5.7.3. Hematopoietic Growth Factors
Primary prophylactic use of granulocyte-colony stimulating factors (G-CSF) is not permitted 
during Cycle 1, but they may be used to treat treatment emergent neutropenia as indicated by 
the current ASCO guidelines. 
Erythropoietin (EPO) may be used at the investigator’s discretion for the supportive 
treatment of anemia. 
5.7.4. Anti Diarrhea, Anti-Emetic Therapy
Primary prophylaxis of diarrhea, nausea and vomiting is permitted in the first and subsequent 
cycles at the investigator’s discretion.  Investigators should follow National Comprehensive 
Cancer Network (NCCN) Guidelines and/or institutional standard operating procedures for 
selection of the prophylactic drug, assuming the drug is not included in the Concomitant 
Treatment(s) section.
5.7.5. Anti-inflammatory Therapy
Anti-inflammatory or narcotic analgesic may be offered as needed assuming there is no 
known or expected drug-drug interaction and assuming the drug is not included in the 
Concomitant Treatment(s) section. 
5.7.6. Corticosteroids
Chronic, systemic corticosteroid use (prednisone 12.5 mg/day or dexamethasone
2 mg/day) for palliative or supportive purpose is not permitted. Acute emergency 
administration, topical applications, inhaled sprays, eye drops or local injections of 
corticosteroids are allowed.
5.7.7. Surgery 
Caution is advised on theoretical grounds for any surgical procedures during the study.  The 
appropriate interval of time between surgery and PF-06647020 required to minimize the risk 
of impaired wound healing and bleeding has not been determined.  Stopping PF-06647020 is
recommended at least 7 days prior to surgery.  Postoperatively, the decision to reinitiate 
PF--06647020 treatment should be based on a clinical assessment of satisfactory wound 
healing and recovery from surgery.


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6. STUDY PROCEDURES 
6.1. Screening
All patients being considered for the study and eligible for screening must provide evidence 
of informed consent for the study before completing any study-specific procedures and may 
be >28 days from first dose.  A patient identification number will be assigned.  The 
investigator (or appropriate delegate at the site) will obtain informed consent from each 
patient in accordance with the procedures described in the Schedule Of Activities and 
Assessments section on Patient Information and Informed Consent.
Patients will be screened within 28 days prior to administration of the study treatment to 
confirm that they meet the patient selection criteria for the study. 
For screening procedures see the Schedule Of Activities and Assessments section.  Following 
completion of the screening assessments and confirmation of eligibility, patients may be 
enrolled. 
6.2. Treatment Period
For treatment period procedures, see Schedule Of Activities and Assessments section.
6.3. Follow-up Visit
For follow-up procedures see Schedule Of Activities and Assessments section.  Patients will 
return to the clinic at least 28 days and no more than 35 days after the end of treatment visit
to undergo review of concomitant medications, vital signs, and assessment for resolution of 
any treatment related toxicity.  Patients continuing to experience toxicity at this point 
following discontinuation of treatment will continue to be followed at least every 4 weeks 
until resolution or determination, in the clinical judgment of the Investigator, that no further 
improvement is expected. 
6.4. Patient Withdrawal
Withdrawal of Consent: Patients who request to discontinue study treatment will remain in 
the study and must continue to be followed for protocol specified follow-up procedures.  The 
only exception to this is when a patient specifically withdraws consent for any further contact 
with him/her or persons previously authorized by patient to provide this information.  
Patients should notify the investigator of the decision to withdraw consent from future 
follow-up in writing, whenever possible.  The withdrawal of consent should be explained in 
detail in the medical records by the investigator, as to whether the withdrawal is from further 
treatment with study drug only or also from study procedures and/or post treatment study 
follow-up, and entered on the appropriate CRF page.  In the event that vital status (whether 
the patient is alive or dead) is being measured, publicly available information should be used 
to determine vital status only as appropriately directed in accordance with local law.
Lost to Follow-Up: All reasonable efforts must be made to locate patients to determine and 
report their ongoing status.  This includes follow-up with persons authorized by the patient as 
noted above.  Lost to follow-up is defined by the inability to reach the patient after a 


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minimum of three documented phone calls, faxes, or emails as well as lack of response by 
patient to one registered mail letter.  All attempts should be documented in the patient’s 
medical records.  If it is determined that the patient has died, the site will use permissible 
local methods to obtain the date and cause of death.  If investigator’s use of third-party 
representative to assist in the follow-up portion of the study has been included in the patient’s 
informed consent, then the investigator may use a Sponsor retained third-party representative 
to assist site staff with obtaining patient’s contact information or other public vital status data 
necessary to complete the follow-up portion of the study.  The site staff and representative 
will consult publicly available sources, such as public health registries and databases, in 
order to obtain updated contact information.  If after all attempts, the patient remains lost to 
follow-up, then the last known alive date as determined by the investigator should be 
reported and documented in the patient’s medical records.
Withdrawal due to disease progression: According to published and internally generated data, 
an ADC may trigger immune responses in NSCLC adenocarcinoma resulting in a “delayed” 
response phenomenon in which the mechanism of the delayed response is to be explored. It 
is possible that a patient with NSCLC adenocarcinoma treated with PF-06647020 could 
demonstrate disease progression at an early time point of response measurement and later 
demonstrate a clinical improvement which could be a result of a delayed response.  In 
scenarios where clinical improvement is seen at the Follow Up Visit and the patient has not 
received any additional anti-cancer therapy since the last dose of study drug, the Investigator 
may discuss with the Sponsor about the possibility of keeping the patient on study and 
resume treatment with the study drug.
The reason for a patient’s discontinuation from treatment will be documented in the end of 
study/withdrawal CRF.  Patients will be followed for at least 28 days after the last dose of 
study drug for adverse events. 
An End of Treatment visit will be conducted at the visit that the patient is discontinued from 
the trial.  Assessments should be obtained if not completed in the last week.  Tumor 
assessments should be performed if not completed in the last 6 weeks. 
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 investigator site. 
Reasons for withdrawal of study treatment may include:

Objective disease progression according to RECIST 1.1;

Global deterioration of health status requiring discontinuation;

Unacceptable toxicity;

Pregnancy;


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
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 the patient to return for a final visit, if applicable 
and follow-up with the patient regarding any unresolved AEs.
If the patient refuses further visits, the patient withdraws consent for disclosure of future 
information or for further contact, no further study specific evaluations should be performed, 
and no additional data should be collected.  The sponsor may retain and continue to use any 
data collected before such withdrawal of consent.
7. ASSESSMENTS
Every effort should be made to ensure that the protocol-required tests and procedures are 
completed as described. However, it is anticipated that from time to time there may be 
circumstances outside of the control of the investigator that may make it unfeasible to 
perform the test. In these cases the investigator will take all steps necessary to ensure the 
safety and well-being of the patient. When a protocol-required test cannot be performed, the
investigator will document the reason for this and any corrective and preventive actions 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 manner.
For samples being collected and shipped, detailed collection, processing, storage, shipment 
instructions and contact information will be provided to the investigator site prior to initiation 
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DDI Sub-Study: See Schedule of Activities (Table A1and Table A2) in Appendix 7 for 
details.
Q2W Regimen Expansion: See Schedule of Activities (Tables A3, A4 and A5) in 
Appendix 8 for details.
7.1. Safety Assessment
Safety assessments will include collection of AEs, SAEs, vital signs and physical 
examination, ECG (12-lead), laboratory assessments, including pregnancy tests and 
verification of 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, will be performed on two occasions prior to starting study 
therapy – once at the start of screening and once on Day 1 of Cycle 1 before investigational
product administration.  Following a negative pregnancy test result at screening, appropriate 
contraception must be commenced and another negative pregnancy test result will then be 
required at the baseline visit before the patient may receive the investigational product.  
Pregnancy tests will be repeated at every treatment cycle during the active treatment period, 
at the end of study treatment and additionally whenever one menstrual cycle is missed or 
when potential pregnancy is otherwise suspected.  Additional pregnancy tests may also be 
undertaken if requested by Institutional Review Boards/Ethics Committees (IRB/EC) or if 
required by local regulations.  In the case of a positive confirmed pregnancy, the patient will 
be withdrawn from study medication but may remain in the study. 
7.1.2. Adverse Events
Assessment of adverse events will include the type, incidence, severity (graded by NCI 
CTCAE version 4.03) timing, seriousness, and relatedness.
7.1.3. Laboratory Safety Assessment
Hematology and blood chemistry will be drawn at the time points described in the Schedule 
Of Activities and analysed at local laboratories.  On Day 1 of Cycle 1, the hematology, 
coagulation, blood chemistry and urinalysis samples do not need to be repeated if the
laboratory screening assessments are performed within 72 hours prior to dosing.  
Hematology and blood chemistry will be collected on Days 1, 4, 8 and 15 of the first cycle.  
For subsequent cycles, hematology and blood chemistry will be collected on Days 1, 8, and 
15 of each cycle.  Beginning at Cycle 8, the Day 8 assessments will be optional for patients 
that have achieved a CR, PR or SD if agreed upon by the treating physician.
Investigators may have additional blood tests performed for the purpose of planning 
treatment administration, dose modification, or following AEs.


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Hematology
Chemistry
Coagulation
Urinalysis
Pregnancy Test
Hemoglobin
ALT/SGPT
PT or INR
Urine dipstick or full 
urinalysis is 
acceptable
For female patients
of childbearing 
potential, serum or 
urine
Platelets
AST/SGOT
PTT
For urine protein: If
WBC
Alk Phos
2+ protein on urine
Absolute Neutrophils
Sodium
dipstick, then collect
Lymphocytes (absolute 
or %)
Potassium
spot urine sample to
Monocytes (absolute 
or %)
Magnesium
calculate urine
Eosinophils (absolute 
or %)
Chloride
protein to creatinine
Basophils (absolute 
or %)
Calcium
ratio (UPCR)
Total Bilirubin***
Total protein
Microscopic analysis 
BUN or Urea
if dipstick abnormal
Creatinine
Uric Acid
Glucose (non-fasted)
Albumin
Phosphorous
Bicarbonate or carbon 
dioxide
LDH
*** 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, alkaline phosphatase, total bile acids and acetaminophen drug and/or protein adduct levels. 
7.1.4. Vital Signs and Physical Examination
Patients will have a physical exam to include weight, vital signs, assessment of ECOG status 
and height; height will be measured at baseline only. 
A full physical examination (PE) will be performed at Screening, Day 1 of Cycle 1, and at 
the End of Treatment visit for each patient and will include an assessment of all body 
systems (including neurological examination, genitourinary examination is optional), the 
measurement of body weight, height (measured at screening only) vital signs and assessment 
of ECOG performance status.  The full PE on Day 1 of Cycle 1 is not required if the 
screening full PE is performed within 1 week of dosing.  Findings of all physical 
examinations should be recorded in the source documents, and any change from baseline 
considered by the investigator to be clinically significant should be recorded as an adverse 
event in the CRF.
Abbreviated PEs should be performed as appropriate at each visit where full physical exams 
are not required, and on an as needed basis for assessment of adverse events.  Abbreviated 
exams should be targeted to specific symptoms or complaints and be consistent with local 
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An eye exam (performed by an ophthalmologist) will be performed at screening.  The eye 
exam includes Best Corrected Visual Acuity (BCVA), Intraocular Pressure (IOP) preferably 
by Goldmann applanation, Biomicroscopic Exam (also called slit lamp exam) to evaluate the 
Lids/Lashes/Adnexae, conjunctiva/sclera, cornea, anterior chamber, iris, lens, and Dilate 
fundus exam to evaluate the optic nerve, the vessels, the macula, the peripheral retina.
Further ophthalmic examinations should be guided by specific ocular signs and symptoms 
should they occur during treatment and follow up. 
Weight and body surface area (BSA) do not need to be performed at each visit; however 
patients should be monitored throughout the study for significant weight change.  If a 
patient’s weight fluctuates by more than 10% in either direction, weight should be collected 
to recalculate the appropriate dose for the next cycle.  In cases where individual 
institution/pharmacy require more frequent weight measurements, weight can be obtained on 
each day of administration, and the dose recalculated.
Vital signs will include measurements of blood pressure, pulse rate and temperature (oral, 
tympanic or axillary).  On Day 1 of each cycle, vital signs should be measured prior to 
infusion start (pre-dose) and 1 hour after the start of the infusion.  Sitting blood pressure (BP) 
will be measured after 5 minutes of rest with the patient’s arm supported at the level of the 
heart and recorded to the nearest mmHg sufficient.  The same arm (preferably the dominant 
arm) should preferably be used throughout the trial.  The blood pressure cuff, which has been 
properly sized and calibrated, should be used to measure blood pressure.  The use of 
automated devices for measuring BP and pulse rate is acceptable.  When the timing of the 
measurements coincides with a blood collection, blood pressure and pulse rate should be 
obtained around to the nominal time of the blood collection.
Beginning at Cycle 8, the Day 8 assessments will be optional for patients that have achieved 
a CR, PR or SD if agreed upon by the treating physician.
7.1.5. (12-Lead) ECG
12-lead ECG will be collected as per the Schedule Of Activities and should be performed 
after the patient has rested quietly for a sufficient amount of time.  ECGs will be compared to 
the patient’s screening ECG and any clinically significant changes will be recorded as 
adverse events and evaluated further, as clinically warranted.  If the mean QTc is prolonged 
(value of >500 msec), the ECGs should be re-evaluated by a qualified person at the 
institution for confirmation.  Additional ECGs should be performed if clinically indicated.
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 should preferably be carried out before or after 
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). 
The following measurements from ECGs will be recorded: QT interval, Heart Rate, RR 
Interval, PR Interval, and QRS Complex.


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Beginning at Cycle 8, Day 8 assessments will be optional for patients that have achieved a 
CR, PR or SD if agreed upon by the treating physician.
7.2. Pharmacokinetics Assessments
Blood samples will be collected from patients for PK analysis as noted in the Schedule Of 
Activities.  All efforts will be made to obtain the PK samples at the scheduled nominal time 
relative to dosing and according to windows provided in the Schedule Of Activities.  
Samples obtained within 10% of the nominal time (eg, within 6 minutes of a 60 minute 
sample) will be considered protocol compliant, and the exact time of the sample collection 
will always be noted on the Case Report Form (CRF).  If a scheduled blood sample 
collection cannot be completed for any reason, the missed sample time may be re-scheduled 
with agreement of clinical investigators, patient and sponsor.  PK samples will be assayed 
using validated analytical methods in compliance with Pfizer standard operating procedures.  
Details regarding the collection, processing, storage, and shipping of the blood samples will 
be provided in the Laboratory Manual.
7.2.1. Serum Sample Collection for PK analysis of ADC (PF-06647020), Total Antibody 
(hu6M024 mAb) and Unconjugated Payload (PF-06380101)
Blood samples (4 mL whole blood) to provide approximately 2 mL of serum for 
measurement of serum PF-06380101 concentrations and blood samples (6 mL whole blood) 
to provide approximately 3 mL of serum for determination of ADC (PF-06647020) and total 
antibody (hu6M024 mAb) concentrations will be collected from patients in dose escalation
and randomized Arms A and C, in appropriately labeled tubes at times specified in the SOA.  
In addition to samples collected at the scheduled times, an additional blood sample should be 
collected from patients experiencing unexpected and/or serious AEs and the date and time 
should be documented in the CRF.
As part of understanding the PK disposition of the study drug, samples may be used for 
possible metabolite identification experiments and/or evaluation of the bioanalytical 
methods.  These data will be used for internal exploratory purpose and will not be included in 
the clinical report.  Samples collected for this purpose will be retained in accordance to local 
regulations and if not consumed during the course of these experiments, will be discarded.
 
  The studies may help in the 
future development of this drug as a single agent, or in combination with other compounds.
 
 
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 Samples will be assayed using a validated analytical method in 
compliance with Pfizer standard operating procedures.  Details regarding the collection 
processing, storage and shipping of the blood samples will be provided in the Study Manual.
7.4. Tumor Response Assessments
Tumor assessments will include all known or suspected disease sites.  Imaging may include 
chest, abdomen and pelvis computed tomography (CT) or magnetic resonance imaging 
(MRI) scans; brain CT or MRI scan for patients with known or suspected brain metastases; 
bone scan and/or bone X-rays for patients with known or suspected bone metastases.  
Baseline CNS imaging is not required with the exception of symptomatic patients to rule out 
central nervous system (CNS) metastases.
The same imaging technique used to characterize each identified and reported lesion at 
baseline will be employed in the subsequent tumor assessments.
CT or MRI scans are to be done every 6 weeks (±5 days) from the start of study treatment 
until disease progression or death, or at the time of withdrawal from treatment (if not done in 
the previous 6 weeks).  The frequency may be reduced to every 12 weeks after 6 months of 
study treatment.  Tumor assessments should be fixed according to the calendar, regardless of 
treatment delays.  For patients enrolled in Part 2, responses of complete response (CR) or 
partial response (PR) must be confirmed by repeat assessment no less than 4 weeks after the 
criteria for response are first met.  Tumor assessments should be repeated at the End of 
Treatment visit if more than 6 weeks have passed since the last evaluation. 
Assessment of response will be made using RECIST version 1.1 (Appendix 2). Changes in
tumor size will be categorized as CR, PR, SD, or PD, the latter incorporating the appearance 
of new lesions. For patients in Part 2, responses of CR or PR must be confirmed by repeat 
assessment no less than 4 weeks after the criteria for response are first met.
All radiographic images will be collected for potential central review. Additional 
information on diagnostic imaging procedures and collection will be included in the 
Imaging Manual.
OVCA patients should have serum samples collected for CA-125 at pre-treatment, each 
tumor assessment (every 6 wks), and end of treatment.  Additional serum samples to be 
collected for assessment of CA-125 as per Investigator discretion.
One of the key elements of this study is the possibility to evaluate potential molecular targets 
that could be modified in vivo by PF-06647020.  
 
  The studies may help in the future development of this drug as a 
single agent, or in combination with other compounds.
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Table 11 summarizes representative assays to be used and the source of the samples.  Refer 
to the Schedule Of Activities for details pertaining to specific days of sample collection and 
to the Study Manual for details of sample preparation.
Table 11.
Pharmacodynamic Summary
Assay
Source
 
 
 
 
mRNA profiling 
 
  
 
 
 
 
 
 Additionally, evaluation of T-cell receptor (TCR) usage, clonality, and frequency via 
TCR sequencing may be performed.
Instructions for sample collection, processing, storage and shipment will be provided in the 
Study Manual.  Samples may be retained in accordance with local regulations and if not used 
within this timeframe, will be destroyed.
7.5.2. Immunophenotyping
 
 Instructions for sample collection, processing, storage and shipment 
will be provided in the Study Manual.  
Samples may be used for flow cytometry assay development.  Samples used for this purpose 
will be retained in accordance with local regulations and if not used within this timeframe, 
will be destroyed.
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7.7. Immunogenicity Assessment
Blood samples (6 mL) to provide approximately 3 mL of serum to detect ADA and 
neutralizing antibody (Nab) against PF-06647020 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 Study Manual.
Samples will be analyzed using a validated analytical method in compliance with Pfizer 
standard operating procedures.  The ADA sample analysis will follow a tiered approach of 
screening, confirmation, and titer determination. Samples tested positive for ADA may also 
be characterized for Nab.
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As part of understanding the immunogenicity of the study drug, 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.
 
 
  Comparing the deoxyribonucleic acid (DNA), 
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. 
 
 
 
 
 
Samples will be kept in a 
facility accessible only by badge-swipe. Data will be stored on password-protected computer 
systems.
 
 
 
 
 
 
 
 
 
 
 
 
  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.
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Detailed collection, processing, storage, and 
shipment instructions are provided in the laboratory manual.
  
Patients will be advised in the informed consent document/patient information sheet that they 
will not be compensated in this event.
 
 
 
 
 
7.9. Other Assessments
7.9.1. Tumor and Medical History
History of the patient’s disease under study including details of the primary diagnosis and 
treatment history will be collected within 28 days before the start of treatment.  In addition, a 
history of disease process other than the cancer under study (active or resolved) and 
concurrent illnesses will be collected.  This will also include prior treatments and any current 
medical treatments for any condition.
7.9.2. Baseline Signs and Symptoms
On Day 1 prior to the start of treatment, patients will be asked about any signs and symptoms 
experienced within the past 14 days.  Baseline signs and symptoms will be recorded on the 
Medical History CRF.
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8. ADVERSE EVENT REPORTING
8.1. Adverse Events
All observed or volunteered AEs regardless of treatment group or suspected causal 
relationship to the investigational product(s) will be reported as described in the following 
sections. 
For all AEs, the investigator must pursue and obtain information adequate both to determine 
the outcome of the AE and to assess whether it meets the criteria for classification as an SAE 
requiring immediate notification to Pfizer or its designated representative.  For all AEs, 
sufficient information should be obtained by the investigator to determine the causality of the 
AE.  The investigator is required to assess causality.  Follow-up by the investigator may be 
required until the event or its sequelae resolve or stabilize at a level acceptable to the 
investigator, and Pfizer concurs with that assessment.
As part of ongoing safety reviews conducted by the sponsor, any nonserious AEs that is 
determined by the sponsor to be serious will be reported by the sponsor as a 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.
8.1.1. 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 nonserious) 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 nonserious 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.
8.1.2. Definition of an Adverse Event
An AE is any untoward medical occurrence in a clinical investigation patient administered a 
product or medical device; the event need not necessarily have a causal relationship with the 
treatment or usage.  Examples of AEs include but are not limited to:

Abnormal test findings;


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
Clinically significant symptoms and signs;

Changes in physical examination findings;

Hypersensitivity;

Drug abuse;

Drug dependency.
Additionally, they may include the signs or symptoms resulting from:

Drug overdose;

Drug withdrawal;

Drug misuse; 

Drug interactions;

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.
8.2. Medication Errors
Medication errors may result, in this study, from the administration or consumption of the 
wrong product, by the wrong patient, at the wrong time, or at the wrong dosage strength.  
Such medication errors occurring to a study participant are to be captured on the medication 
error CRF which is a specific version of the AE page, and on the SAE form when 
appropriate.  In the event of medication dosing error, the sponsor should be notified 
immediately.
Medication errors are reportable irrespective of the presence of an associated AE/SAE, 
including:

Medication errors involving patient exposure to the investigational product;

Potential medication errors or uses outside of what is foreseen in the protocol that do 
or do not involve the participating patient.


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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 adverse event(s) are captured on an adverse event AE CRF 
page.
8.2.1. Abnormal Test Findings
The criteria for determining whether an abnormal objective test finding should be reported as 
an AE are as follows: 

Test result is associated with accompanying symptoms; and/or

Test result requires additional diagnostic testing or medical/surgical intervention;
and/or

Test result leads to a change in study dosing (outside of protocol-stipulated dose 
adjustments) or discontinuation from the study, significant additional concomitant 
drug treatment, or other therapy; and/or

Test result is considered to be an AE by the investigator or sponsor.
Merely repeating an abnormal test, in the absence of any of the above conditions, does not 
constitute an AE.  Any abnormal test result that is determined to be an error does not require 
reporting as an AE.
8.2.2. Serious Adverse Events
An SAE is any untoward medical occurrence at any dose that:

Results in death;

Is life-threatening (immediate risk of death);

Requires inpatient hospitalization or prolongation of existing hospitalization;

Results in persistent or significant disability/incapacity (substantial disruption of the 
ability to conduct normal life functions);

Results in congenital anomaly/birth defect;

Progression of the malignancy under study (including signs and symptoms of 
progression) should not be reported as an SAE unless the outcome is fatal within the 
safety reporting period.  Hospitalization due to signs and symptoms of disease 
progression should not be reported as an SAE.  If the malignancy has a fatal outcome 
during the study or within the safety reporting period, then the event leading to death 
must be recorded as an AE and as an SAE with NCI CTCAE grade 5 (see Section on 
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Medical and scientific judgment is exercised in determining whether an event is an important 
medical event.  An important medical event may not be immediately life-threatening and/or 
result in death or hospitalization.  However, if it is determined that the event may jeopardize 
the patient or may require intervention to prevent one of the other AE outcomes, the 
important medical event should be reported as serious.
Examples of such events are intensive treatment in an emergency room or at home for 
allergic bronchospasm; blood dyscrasias or convulsions that do not result in hospitalization; 
or development of drug dependency or drug abuse.
8.2.3. Protocol-Specified Serious Adverse Events
There are no protocol-specified SAEs in this study.  All SAEs will be reported by the 
investigator as described in previous sections and will be handled as SAEs in the safety 
database (see Section on Serious Adverse Event Reporting Requirements).
8.2.4. Potential Cases of Drug-Induced Liver Injury 
Abnormal values in AST and/or ALT levels concurrent with abnormal elevations in total 
bilirubin level that meet the criteria outlined below in the absence of other causes of liver 
injury are considered potential cases of drug-induced liver injury (potential Hy’s law cases) 
and should always be considered important medical events. 
The threshold of laboratory abnormalities for a potential case of drug-induced liver injury 
depends on the patient’s individual baseline values and underlying conditions. Patients who 
present with the following laboratory abnormalities should be evaluated further to 
definitively determine the etiology of the abnormal laboratory values:

Patients with AST or ALT and total bilirubin baseline values within the normal range 
who subsequently present with AST or ALT values 3 times the upper limit of 
normal (X ULN) concurrent with a total bilirubin value 2 X ULN with no evidence 
of hemolysis and an alkaline phosphatase value 2 X ULN or not available;

For patients with preexisting ALT OR AST OR total bilirubin values above the ULN, 
the following threshold values should be used in the definition mentioned above:

For patients with preexisting AST or ALT baseline values above the normal range,
AST or ALT value 2 times the baseline values and 3 X ULN, or 8 X ULN
(whichever is smaller);
Concurrent with

For patients with pre-existing values of total bilirubin above the normal range: Total 
bilirubin level increased from baseline by an amount of at least 1 X ULN or if the 
value reaches 3 X ULN (whichever is smaller).


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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, PT/ INR, and 
alkaline phosphatase.  A detailed history, including relevant information, such as review of 
ethanol, acetaminophen, recreational drug and supplement consumption, family history, 
occupational exposure, sexual history, travel history, history of contact with a jaundiced 
person, surgery, blood transfusion, history of liver or allergic disease, and work exposure, 
should be collected. Further testing for acute hepatitis A, B, or C infection and liver imaging 
(eg, biliary tract) may be warranted. All cases confirmed on repeat testing as meeting the 
laboratory criteria defined above, with no other cause for liver function test (LFT)
abnormalities identified at the time, should be considered potential Hy’s Law cases 
irrespective of availability of all the results of the investigations performed to determine 
etiology of the abnormal LFTs. Such potential Hy’s law cases should be reported as SAEs.
8.2.5. 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 a hospitalization; 
however, the event leading to the emergency room visit should be assessed for medical 
importance.
Hospitalization does not include the following:

Rehabilitation facilities;

Hospice facilities;

Respite care (eg, caregiver relief);

Skilled nursing facilities;

Nursing homes;

Same-day surgeries (as outpatient/same day/ambulatory procedures).
Hospitalization or prolongation of hospitalization in the absence of a precipitating, clinical 
AE is not in itself an SAE.  Examples include: 

Admission for treatment of a preexisting condition not associated with the 
development of a new AE or with a worsening of the preexisting condition (eg, for 
workup of persistent pre-treatment laboratory abnormality);


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
Social admission (eg, patient has no place to sleep);

Administrative admission (eg, for yearly physical examination);

Protocol-specified admission during a study (eg, for a procedure required by the study 
protocol);

Optional admission not associated with a precipitating clinical AE (eg, for elective 
cosmetic surgery);

Hospitalization for observation without a medical AE;

Preplanned treatments or surgical procedures.  These should be noted in the baseline 
documentation for the entire protocol and/or for the individual patient;

Admission exclusively for the administration of blood products.
Diagnostic and therapeutic noninvasive and invasive procedures, such as surgery, should not 
be reported as AEs.  However, the medical condition for which the procedure was performed 
should be reported if it meets the definition of an AE.  For example, an acute appendicitis 
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.
8.3. Severity Assessment
GRADE
Clinical Description of Severity
0
No Change from normal or reference range (This grade is not included in the NCI 
CTCAE Version 4.03 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.
8.3.1. Causality Assessment
The investigator’s assessment of causality must be provided for all AEs (serious and 
nonserious); 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 


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AE; generally the facts (evidence) or arguments to suggest a causal relationship should be 
provided.  If the investigator does not know whether or not the investigational product caused 
the event, then the event will be handled as “related to investigational product” for reporting 
purposes, as defined by the sponsor (see section on Reporting Requirements).  If the 
investigator's causality assessment is “unknown but not related to investigational product,”
this should be clearly documented on study records. 
In addition, if the investigator determines that an SAE is associated with study procedures, 
the investigator must record this causal relationship in the source documents and CRF, as 
appropriate, and report such an assessment in accordance with the SAE reporting 
requirements, if applicable.
8.3.1.1. Exposure During Pregnancy
For both unapproved/unlicensed products and for marketed products, an exposure during 
pregnancy occurs if:

A female becomes, or is found to be, pregnant either while receiving or having been 
exposed (eg, because of treatment or environmental exposure) to the investigational 
product; or the female becomes, or is found to be pregnant after discontinuing and/or 
being exposed to the investigational product;

An example of environmental exposure would be a case involving direct contact 
with a Pfizer product in a pregnant woman (eg, a nurse reports that she is pregnant 
and has been exposed to chemotherapeutic products).

A male has been exposed (eg, because of treatment or environmental exposure) to the 
investigational product prior to or around the time of conception and/or is exposed 
during his partner’s pregnancy.
If a study patient or study patient’s partner becomes or is found to be pregnant during the 
study patient’s treatment with the investigational product, the investigator must submit this 
information to the Pfizer drug safety unit on a Serious Adverse Event (SAE) Report Form 
and Exposure During Pregnancy (EDP) supplemental form, regardless of whether an SAE 
has occurred.  In addition, the investigator must submit information regarding environmental 
exposure to a Pfizer product in a pregnant woman (eg, a patient reports that she is pregnant 
and has been exposed to a cytotoxic product by inhalation or spillage) using the EDP 
supplemental form.  This must be done irrespective of whether an AE has occurred and 
within 24 hours of awareness of the exposure.  The information submitted should include the 
anticipated date of delivery (see below for information related to termination of pregnancy).
Follow-up is conducted to obtain general information on the pregnancy and its outcome for 
all EDP reports with an unknown outcome.  The investigator will follow the pregnancy until 
completion (or until pregnancy termination) and notify Pfizer of the outcome as a follow-up 
to the initial EDP supplemental form.  In the case of a live birth, the structural integrity of the 
neonate can be assessed at the time of birth.  In the event of a termination, the reason(s) for 
the termination should be specified and, if clinically possible, the structural integrity of the 


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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.
Additional information about pregnancy outcomes that are reported as SAEs follows: 

Spontaneous abortion includes miscarriage and missed abortion;

Neonatal deaths that occur within 1 month of birth should be reported, without regard 
to causality, as SAEs.  In addition, infant deaths after 1 month should be reported as 
SAEs when the investigator assesses the infant death as related or possibly related to 
exposure to the investigational product.
Additional information regarding the exposure during pregnancy may be requested by the 
investigator.  Further follow-up of birth outcomes will be handled on a case-by-case basis 
(eg, follow-up on preterm infants to identify developmental delays).  In the case of paternal 
exposure, the investigator will provide the study patient with the Pregnant Partner Release of 
Information Form to deliver to his partner.  The investigator must document in the source 
documents that the patient was given the Pregnant Partner Release of Information Form to 
provide to his partner
8.3.1.2. Occupational Exposure
An occupational exposure occurs when during the performance of job duties, a person 
(whether a healthcare professional or otherwise) gets in unplanned direct contact with the 
product, which may or may not lead to the occurrence of an adverse event.
An occupational exposure is reported to 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.
8.4. 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 a SAE, the SAE must be reported in accordance with 
the reporting requirements defined below.
8.4.1. 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.


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8.5. Reporting Requirements
Each AE is to be assessed to determine if it meets the criteria for SAEs.  If an SAE occurs, 
expedited reporting will follow local and international regulations, as appropriate.
8.5.1. 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 exposure during pregnancy, exposure via 
breastfeeding and occupational exposure cases. 
In the rare event that the investigator does not become aware of the occurrence of an SAE 
immediately (eg, if an outpatient study patient initially seeks treatment elsewhere), the 
investigator is to report the event within 24 hours after learning of it and document the time 
of his or her first awareness of the AE.
For all SAEs, the investigator is obligated to pursue and provide information to Pfizer in 
accordance with the time frames for reporting specified above.  In addition, an investigator 
may be requested by Pfizer to obtain specific additional follow-up information in an
expedited fashion.  This information collected for SAEs is more detailed than that captured 
on the AE CRF.  In general, this will include a description of the AE in sufficient detail to 
allow for a complete medical assessment of the case and independent determination of 
possible causality.  Information on other possible causes of the event, such as concomitant 
medications, vaccines, and/or illnesses, must be provided.  In the case of a patient death, a 
summary of available autopsy findings must be submitted as soon as possible to Pfizer or its 
designated representative. 
8.5.2. 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.
8.5.3. 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.


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9. DATA ANALYSIS/STATISTICAL METHODS
Detailed methodology for summary and statistical analyses of the data collected in this study 
is outlined here and further detailed in a statistical analysis plan (SAP), which will be 
maintained by the sponsor.  This SAP may modify what is outlined in the protocol where 
appropriate; however, any major modifications of the primary endpoint definitions or their 
analyses will also be reflected in a protocol amendment.
Additional details of the analyses will be provided in the clinical study report (CSR).  This 
information may include details of missing and, if applicable, unused and spurious data.  
Deviations from the statistical plan will be reported in the clinical study report.
9.1. Analysis sets 
Data analyses will be performed on the following analysis population.
1. Safety analysis set.

The safety analysis set includes all enrolled patients who receive at least one dose of 
study medication.
2. Full analysis set.

The full analysis set includes all enrolled patients.
3. Per protocol analysis set (evaluable for MTD).

The per protocol analysis set includes all enrolled patients who receive at least one 
dose of study medication and who do not have major treatment deviations during first 
cycle. Patients with major treatment deviations in the DLT observation period are not 
evaluable for the MTD assessment and will be replaced as needed to permit MTD 
estimation. Major treatment deviations include:

Administration of less than 33% of the planned dose of 
PF-06647020 (provided that the reduction is not due to toxicity attributable to 
PF-06647020;

Administration of more than 33% of the planned dose of PF-06647020 failure to 
satisfy major entry criteria (eg, confirmation of the target disease, signed 
informed consent);

Use of other anticancer treatments during the active treatment and disease follow 
up phases other than as defined/allowed in this protocol;

A baseline disease assessment and at least one post-baseline disease assessment.


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4. PK analysis sets.
•
The PK parameter analysis population is defined as patients who receive at least 
1 dose of study treatment and have sufficient information to estimate at least 1 of the 
PK parameters of interest.
5. Immunogenicity analysis set.
•
The immunogenicity analysis set is defined as patients who receive at least 1 dose of 
study treatment and have at least 1 ADA sample collected.
6.
 
 
7.
 
9.2. Statistical Methods and Properties
This study is designed to establish the MTD defined as the dose that yields approximately 
25% probability of DLT and considers equivalent doses that yield probability of DLT in the 
interval (Equivalence Interval) 20% to 30%.  The 25% target was chosen based on safety 
considerations. The prior distribution of DLT is set as a beta (0.75, 0.65), and the threshold 
probability for early termination and dose exclusion is set to 0.975. Doses with an incidence 
of DLT ≥33% cannot be selected as MTD although is allowed by the mTPI method.
9.2.1. Statistical Methods for Dose Escalation/De-Escalation
The modified toxicity probability interval (mTPI) design8 uses a Bayesian statistics 
framework and a beta/binomial hierarchical model to compute the posterior probability of 
three dosing intervals that reflect the relative difference between the toxicity rate of each 
dose level to the target rate (pT = 0.25). If the toxicity rate of the currently used dose level is 
far smaller than pT, the mTPI will recommend escalating the dose level; if it is close to target 
probability (pT), the mTPI will recommend continuing at the current dose; if it is far greater 
than pT, the mTPI will recommend de-escalating the dose level. These rules are 
conceptually similar to those used by the 3+3 design, except the decisions of an mTPI design 
are based on posterior probabilities calculated under a coherent probability model. 
Being a model-based design, mTPI automatically and appropriately tailors dose-escalation 
and de-escalation decisions for different studies with different toxicity parameters. More 
importantly, all the dose-escalation decisions for a given study can be pre-calculated under 
the mTPI design and presented in a two-way table as shown in Table 8. Thus, compared to 
other advanced model-based designs published in the literature, the mTPI design is 
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logistically less complicated and easier to implement. Recently, a phase I study based on the 
mTPI design has been published.6
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.  Based on the 
safety profile of PF-06647020 as a single-agent, e1 is selected as 0.05, and e2 is selected as 
0.05. Therefore, the target interval for the DLT rate is (0.20, 0.30).
The three dosing intervals are associated with three different dose-escalation decisions. 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 (R). 
Given a dosing interval and a probability distribution, the unit probability mass (UPM) of 
that dosing interval is defined as the probability of a patient belonging to that dosing interval 
divided by the length of the dosing interval. The mTPI design calculates the UPMs for the 
three dosing intervals, and the one with the largest UPM informs the corresponding 
dose-finding decision, which is the dose level to be used for future patients. For example, if 
the under-dosing interval has the largest UPM, the decision will be to escalate, and the next 
cohort of patients will be treated at the next higher dose level8 have demonstrated that the 
decision based on UPM is optimal in that it minimizes a posterior expected loss (ie, 
minimizes the chance of making a wrong dosing decision). 
The dose-finding portion of the study is terminated when either approximately 40 DLT 
evaluable patients have been enrolled or when at least 9 evaluable patients have been treated 
at the highest dose with DLT rate <30%, whichever comes first.
The following table shows the probability of escalating to the next dose level for a range of 
underlying true DLT rates.  For example, for a cohort size of n=3 and for a DLT that occurs 
in 10% of patients, there is a greater than 90% probability of escalating.  Conversely, for a 
DLT that occurs with a rate of 70%, the probability of escalating is 3%.  It is assumed that 
dose escalation occurs with either 0/3 or 1/6 patients with DLTs.
Table 12.
Escalation Probability
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. Statistical Method for Estimating the MTD
As previously described, the estimated MTD is the highest tested dose level with DLT rate 
<0.30 in at least 9 DLT evaluable patients. We assume that higher doses of 
PF-06647020 result in higher toxicity rates.  But, due to the relatively low number of patients 
that may be potentially allocated to any dose combination, this assumption may be violated.


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9.3. Sample Size Determination
Approximately 190 patients are expected to be enrolled in this study, which includes 
approximately 72 patients for the Q2W Regimen Expansion in Amendment 7.
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 40 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.  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. 
The sample size in Part 2 is based on clinical consideration, rather than statistical 
justification.  Upon identification of the MTD by the mTPI method, approximately 
22 patients with TNBC, 45 patients with OVCA and 20 patients with NSCLC will be 
enrolled in Part 2 to further evaluate safety and preliminary efficacy parameters.
9.4. Efficacy Analysis
In this First in Patient study anti-tumor activity is a secondary objective.
Tumor response will be presented in the form of patient data listings that include, but are not 
limited to, tumor type, starting dose, tumor measurements, tumor response at each visit, and 
best overall response.
Objective tumor response, as assessed using the RECIST version 1.1 by calculating the 
Overall (OR), Duration of Response Rate (ORR) and(DoR), DCR, Time to Progression 
(TTP), as determined by Investigator [As assessed by RECIST version 1.1], PFS, OS and 
clinical benefit response rate will be summarized and presented if data permits.
9.4.1. 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 tumor assessment.  Patients must also present with 
measureable disease.
The best overall response is the best response recorded from first dose until disease 
progression/recurrence (taking as reference for PD the smallest measurements recorded since 
screening).  In general, the patient's best response assignment will depend on the 
achievement of both measurement and confirmation criteria.  All measurements (or “too 
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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 tumor measurements must be confirmed by 
repeat assessments that should be performed no less than 4 weeks after the criteria for 
response are first met.  
Clinical benefit response (CBR) is defined as a CR, PR, or SD lasting for ≥6 cycles.
9.5. Analysis of Other Endpoints
  
Data will also be displayed graphically, where appropriate.  
 
 Additional details of the analyses 
are outlined in the SAP.
9.5.1. Analysis of Pharmacokinetics
 
 
  PK parameters will be determined from the 
respective concentration-time data using standard noncompartmental methods.  Actual 
sample collection times will be used for the parameter calculations.  For ADC 
(PF-06647020) and total antibody (hu6M024 mAb), PK parameters including maximum 
concentration (Cmax), time to maximum concentration (Tmax), area under the 
concentration-time curve over 1 dosing interval (AUCτ), area under the concentration-time 
curve from time 0 to the last measurable concentration (AUClast), and if data permit or if 
considered appropriate, area under the concentration-time curve from time 0 extrapolated to 
infinity time (AUCinf), terminal elimination half-life (t½), clearance (CL), volume of 
distribution at steady state (Vss), and accumulation ratio (Rac) will be calculated.  For 
unconjugated payload (PF-06380101), PK parameters including Cmax, Tmax, AUClast, AUCinf, 
AUCτ, t½, and Rac will be calculated as appropriate.  For avelumab, PK parameters including 
Cmax, Tmax, AUClast, AUCinf, AUCτ, t½, CL, Vss and Rac will be calculated as appropriate.
Drug concentrations of ADC (PF-06647020), total antibody (hu6M024 mAb), unconjugated 
payload (PF-06380101), and avelumab will be summarized graphically and with descriptive 
statistics by dose/regimen/treatment, cycle, and the nominal PK sampling time.  
Noncompartmental PK parameters will be summarized descriptively by 
dose/regimen/treatment and cycle.  
9.5.2. Pharmacokinetic/Pharmacodynamic Analysis
Safety (eg, DLT, platelet count) and efficacy (ORR) data from both Part 1 and Part 2 will be 
pooled.  PK/PD analyses will be conducted to explore the exposure-response relationship 
using appropriate model-based methods to assist MTD estimation.
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 PK/PD analysis using 
appropriate model-based methods will be explored to better understand the 
exposure-response relationship and results may be reported separately.
9.5.3. Analysis of Immunogenicity Data 
For the immunogenicity data, the percentage of patients with positive ADA and Nab each 
will be summarized by dose level (Part 1) or by treatment arms (Part 2). For patients with 
positive ADA or neutralizing antibodies, the magnitude (titer), time of onset, and duration of 
ADA or neutralizing antibodies response will also be described, if data permit. 
Potential impact of immunogenicity on PK and 
 
safety/tolerability and efficacy of PF-06647020 will be explored, if data is warranted.
9.6. Safety Analysis
Summaries and analyses of safety parameters will include all patients in the Safety Analysis 
Set.
AEs will be presented with and without regard to causality based on the investigator’s 
judgment.  The frequency of overall toxicity, categorized by toxicity Grades 1 through 5, will 
be described.  Additional summaries will be provided for AEs that are observed with higher 
frequency.
Adverse events, ECGs, blood pressure, pulse rate, 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 examination 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 examinations 
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.
9.6.1. Analysis of Primary Endpoint
DLT is the primary endpoint of the dose escalation component of the study.  The occurrence 
of DLTs observed in the dosing cohorts is used to estimate the MTD as described in the 
Study Design section.  Adverse Events constituting DLTs will be listed per dose level.  
Because the intent is to find a desirable dose that meets the tolerability criteria based on DLT 
rate while demonstrating clinical activity based on response rate, descriptive statistics 
(n, frequency and percentage) will be reported.  Corresponding listings of data will be 
generated.
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9.6.2. Analysis of Secondary Safety Endpoints
9.6.2.1. Adverse Events
AEs will be graded by the investigator according to 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 medication.  The number and percentage of patients who 
experienced any AE, SAE, treatment related AE, and treatment related SAE will be 
summarized according to worst toxicity grades.  The summaries will present AEs both on the 
entire study period and by cycle (Cycle 1 and Cycles beyond 1). 
9.6.2.2. Laboratory Tests Abnormalities
The number and percentage of patients who experienced laboratory test abnormalities will be 
summarized according to worst toxicity grade observed for each lab assay.  The analyses will 
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. 
9.6.3. ECG
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: 
Table 13.
Safety QTcF
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.
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 QTcF value 500 msec, 
but the mean of the triplicates is not 500 msec, the data from the patient’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 QTcF post dose and the pre-dose value on Day 1.
9.7. 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 SAEs according to regulatory guidelines;

Discussions between the investigators and the sponsor of AEs and laboratory tests 
alterations seen at each dose level in an on-going manner at regular teleconferences 
and/or meetings to determine the safety profile and risk/benefit ratio and decide if 
further enrollment is appropriate.
10. QUALITY CONTROL AND QUALITY ASSURANCE
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 investigator site may be subject to 
review by the IRB/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 investigator site for the inspection and will allow Pfizer or its 
agent, whenever feasible, to be present during the inspection.  The investigator site and 
investigator will promptly resolve any discrepancies that are identified between the study 
data and the patient's medical records.  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.
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.


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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 chart.  In these cases,
data collected on the CRFs must match the data in those charts. 
In some cases, the CRF may also serve as source documents.  In these cases, a document 
should be available at the investigator site and at Pfizer that clearly identifies those data that 
will be recorded on the CRF, and for which the CRF will stand as the source document.
11.2. Record Retention
To enable evaluations and/or inspections/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, according to local regulations, or as 
specified in the clinical study agreement (CSA), whichever is longer.
If the investigator becomes unable for any reason to continue to retain study records for the 
required period (eg, retirement, relocation), Pfizer should be prospectively notified.  The 
study records must be transferred to a designee acceptable to Pfizer, such as another 
investigator, another institution, or 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.


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12. ETHICS
12.1. Institutional Review Board (IRB)/Ethics Committee (EC)
It is the responsibility of the investigator to have prospective approval of the study protocol, 
protocol amendments, informed consent documents, and other relevant documents, eg, 
recruitment advertisements, if applicable, from the IRB/EC.  All correspondence with the 
IRB/EC should be retained in the investigator file.  Copies of IRB/EC approvals should be 
forwarded to Pfizer.
The only circumstance in which an amendment may be initiated prior to IRB/EC approval is 
where the change is necessary to eliminate apparent immediate hazards to the patients.  In 
that event, the investigator must notify the IRB/EC and Pfizer in writing immediately after 
the implementation.
12.2. Ethical Conduct of the Study
The study will be conducted in accordance with the protocol, legal and regulatory 
requirements and the general principles set forth in the International Ethical Guidelines for 
Biomedical Research Involving Human Subjects (Council for International Organizations of 
Medical Sciences 2002), ICH Guidelines for Good Clinical Practice, and the Declaration of 
Helsinki. 
12.3. Patient Information and Consent
All parties will ensure protection of patient personal data and will not include patient names 
or other identifiable data in any reports, publications, or other disclosures, except where 
required by law.
When study data is compiled for transfer to Pfizer and other authorized parties, patient
names, addresses, and other identifiable data will be replaced by numerical codes based on a 
numbering system provided by Pfizer in order to de-identify study patients.  The investigator 
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 patient personal data consistent 
with applicable privacy laws.
The informed consent documents and any patient recruitment materials 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 and any patient 
recruitment materials must be reviewed by Pfizer, approved by the IRB/EC before use, and 
available for inspection.
The investigator must ensure that each study patient, or his/her legally acceptable 
representative, is fully informed about the nature and objectives of the study and possible 
risks associated with participation. 


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Whenever consent is obtained from a patient’s legally acceptable representative the patient’s 
assent (affirmative agreement) must subsequently be obtained when the patient has the 
capacity to provide assent, as determined by the IRB/EC.  If the investigator determines that 
a patient’s decisional capacity is so limited he or she cannot reasonably be consulted, then, as 
permitted by the IRB/EC and consistent with local regulatory and legal requirements, the 
patient’s assent may be waived with source documentation of the reason assent was not 
obtained.  If the study patient does not provide his or her own consent, the source documents 
must record why the patient did not provide consent (eg, minor, decisionally impaired adult), 
how the investigator determined that the person signing the consent was the patient’s legally 
acceptable representative, the consent signer’s relationship to the study patient (eg, parent, 
spouse), and that the patient’s assent was obtained or waived.  If assent is obtained verbally, 
it must be documented in the source documents.
The investigator, or a person designated by the investigator, will obtain written informed 
consent from each patient or the patient's legally acceptable representative, before any 
study-specific activity is performed. The investigator will retain the original of each patient's
signed consent document.
12.4. 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 
regulatory 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 All Participating Countries 
End of Trial in all participating countries is defined as Last Patient Last Visit.
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-06647020 at any time.
If a study is prematurely terminated, Pfizer will promptly notify the investigator.  After 
notification, the investigator must contact all participating patients and the hospital pharmacy 
(if applicable) within a reasonable period of time.  As directed by Pfizer, all study materials 
must be collected and all CRFs completed to the greatest extent possible.


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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 (PCD) 
for studies in adult populations or within 6 months of the PCD for studies in pediatric 
populations.
PCD 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 pre-specified protocol or was terminated.
EudraCT
Pfizer posts European Union (EU) Basic Results on EudraCT for all Pfizer-sponsored 
interventional studies that are in scope of EU requirements.  EU Basic Results are submitted 
for posting within 1 year of the PCD for studies in adult populations or within 6 months of 
the PCD for studies in pediatric populations.
www.pfizer.com
Pfizer posts Public Disclosure Synopses (CSR 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 (PI) of the results of the study based on information collected or 
generated by PI, 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.


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The investigator will provide any publication to Pfizer at least 30 days before it is 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 multicenter study, the investigator agrees that the first publication is 
to be a joint publication covering all investigator sites, and that any subsequent publications 
by the PI 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, the Institution will comply with recognized ethical 
standards concerning publications and authorship, including Section II - “Ethical 
Considerations in the Conduct and Reporting of Research” of the Uniform Requirements for 
Manuscripts Submitted to Biomedical Journals, http://www.icmje.org/index.html#authorship,
established by the International Committee of Medical Journal Editors.
Publication of study results is also provided for in the CSA between Pfizer and the 
institution.  In this section entitled Publications by Investigators, the defined terms shall have 
the meanings given to them in the CSA.
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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16. REFERENCES
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Factors: An Evidence-Based Clinical Practice Guideline. JCO Jul 1, 2006:3187-3205
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W, Harbeck N. PTK7 expression in triple-negative breast cancer: Anticancer Res 2013; 
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Bin-Nun N, Lichtig H, Malyarova A, et al. PTK7 modulates Wnt signaling activity via 
LRP6. Development 2014; 141(2):410-21.
4.
Boudeau J, Miranda-saavedra D, Barton GJ, et al. Emerging roles of pseudokinases. 
Trends Cell Biol 2006; 16(9):443-52.
5.
DeRose YS, Wang G, Lin YC, et al. Tumor grafts derived from women with breast 
cancer authentically reflect tumor pathology, growth, metastasis and disease outcomes. 
Nat Med 2011; 17(11):1514-20.
6.
Fanale M, Fayad L, Pro B, et al. Phase I study of bortezomib plus ICE (BICE) for the 
treatment of relapsed/refractory Hodgkin lymphoma. Br J Haematol 2011; 154:284-286
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Hayes M, Naito M, Daulat A, et al. PTK7 promotes non-canonical Wnt/PCP-mediated 
morphogenesis and inhibits Wnt/β-catenin-dependent cell fate decisions during 
vertebrate development. Development 2013; 140(8):1807-18.
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Ji Y, Wang SJ. Modified toxicity probability interval design: a safer and more reliable 
method than the 3+3 design for proactical phase I trials. J Clin Oncol 2013; 
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Meng L, Sefah K, O’Donoghue MB, et al. Silencing of PTK7 in colon cancer cells: 
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Mullard A. Maturing antibody-drug conjugate pipeline hits 30. Nature Reviews Drug 
Discovery 2013;12:329-332.
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Peradziryi H, Tolwinski NS, Borchers A. The many roles of PTK7: a versatile regulator 
of cell-cell communication. Arch Biochem Biophys 2012; 524(1):71-6.
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Prebet T, Lhoumeau AC, Amoulet C, et al. The cell polarity PTK7 receptor acts as a 
modulator of the chemotherapeutic response in acute myeloid leukemia and impairs 
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Sapra P, Hooper AT, O’Donnell CJ, et al.  Investigational antibody drug conjugates for 
solid tumors. Expert Opin. Investig. Drugs 2011; 20(8):1131-49.


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14.
Turner T, Jackson WH, Petit GR, et al. Treatment of human prostate cancer cells with 
dolastatin 10, a peptide isolated from a marine shell-less mollusk. Prostate 1998; 
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Jemal A, Bray F, Center MM, et. al.  Global cancer statistics. CA Cancer J Clin 2011; 
61:69-90.
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Naumann RW and Coleman RL.  Management strategies for recurrent 
platinum-resistant ovarian cancer.  Drugs 2011;71:1397-1412.
17.
Myrand SP, Sekiguchi K, Man MZ, et al. Pharmacokinektics/Genotype Association for 
Major Cytochrome P450 Enzymes in Native and First- and Third-generation Japanese 
Populations: Comparison With Korean, Chinese, and Caucasian Populations. Clin 
Pharmacol Ther. 2008; 84(3):347-61.
18.
Rustin GJ, Vergote I, et. al. Definitions for Response and Progression in Ovarian 
Cancer Clinical Trials incorporating RECIST 1.1 and CA-125 Agreed by the 
Gynecological Cancer Intergroup (GCIG).  Int J Gynecol Cancer 2011; 21:419-423.
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Damelin M, Bankovich A, Bernstein J, et. al. A PTK7-targeted antibody-drug conjugate 
reduces tumor-initiating cells and induces sustained tumor regressions. Sci Transl Med. 
2017 Jan 11;9(372). pii: eaag2611. doi: 10.1126/scitranslmed.aag2611. 
PMID: 28077676.
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Investigator’s Brochure of avelumab (MSB0010718C), Version 3, dated February 2015.
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Mathios D, Kim JE, et al. Anti-PD-1 antitumor immunity is enhanced by local and 
abrogated by systemic chemotherapy in GBM.Sci Transl Med 2016; 8(370):370ra180.
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Investigator’s Brochure of PF-06647020, Version 3, dated August 2016.
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inhibits T cell activation. Nat Immunol 2001; 2(3):261-68.
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Hodi FS, Bulter M, Oble DA, Seiden MV, haluska FG, Kruse A, et al. Immnologic and 
clinical effects of antibody blockade of cytotoic T lymphocyte-associated antigen 4 in 
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Hoos A, Egermont AM, Janetzki S, et al. Improved endpoints for cancer 
immunotherapy trials. J Natl Cancer Inst 2010; 102(18):1388-97.
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Nishino M, Jagannathan JP, Krajewski KM, O’Regan K, Hatabu H,Shapiro G, et al. 
Personalized tumor response assessment in the era of molecular medicine: 
cancer-specific and therapy-specific response criteria to complement pitfalls of 
RECIST. AJR Am J Roentgenol 2012;198:737–45.


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27.
Wolchok JD, et al.: Guidelines for the Evaluation of Immune Therapy Activity in Solid 
Tumors: Immune-Related Response Criteria, Clin Cancer Res 2009; 15(23):7412-7420.
28.
Nishino M, Gargano M, Suda M, Ramaiya NH, Hodi FS. Optimizing immune-related 
tumor response assessment: does reducing the number of lesions impact response 
assessment in melanoma patients treated with ipilimumab?  J Immunother Cancer 
2014;2:17.
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Wang DD, et al.: Fixed dosing versus body size-based dosing of monoclonal antibodies 
in adult clinical trials. J Clin Pharmacol 2009 Sep;49(9):1012-24.
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Gangadhar et al.: Population pharmacokinetic (popPK) model of pembrolizumab 
(pembro; MK-3475) in patients (pts) treated in KEYNOTE-001 and KEYNOTE-002. 
J Clin Oncol 33, 2015 (suppl; abstr 3058).
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Zhao, et al.: Assessment of nivolumab (Nivo) benefit-risk profile from a 240-mg flat 
dose veruss a 3-mg/kg dosing regimen in patients (Pts) with solid tumors. Ann Oncol 
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Hamanishi J, et al.: Programmed cell death 1 ligand 1 and tumor-infiltrating CD8+ T 
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A. 2007 Feb 27;104(9):3360-5. Epub 2007 Feb 21.


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Appendix 1. Abbreviations
This is a list of abbreviations that may be used in the protocol.
Abbreviation
Term
ADA
Anti-drug Antibody
ADC
Antibody Drug Conjugate
ADCC
Antibody dependent cell mediated cytotoxicity
ADR
Adverse Drug Reaction
AE
Adverse Event
AIDS
Acquired Immunodeficiency Syndrome
ALK
Anaplastic Lymphoma Kinase
ALT
Alanine Aminotransferase
AML
Acute Myeloid Leukemia
ANC
Absolute Neutrophil Count
ASCO
American Society of Clinical Oncology
AST
Aspartate Aminotransferase
AUC
Area Under the Curve
Aur0101
Auristatin
BBS
Biospecimen Banking System
BCVA
Best Corrected Visual Acuity
BID
Twice Daily
BOR
Best Overall Response
BP
Blood Pressure
C1D1
Cycle 1 Day 1
CBC
Complete Blood Count
CBR
Clinical Benefit Response
CD8
Cluster of Differentiation 8
CDC
Complement Mediated Cytotoxicity
CK
Creatine Kinase
CL
Clearance
CLIA
Clinical Laboratory Improvement Amendments
CNS
Central Nervous System
COPD
Chronic Obstructive Pulmonary Disease
CR
Complete Response
CRF
Case Report Form
CRO
Contract Research Organization
CSA 
Clinical Study Agreement
CSC 
Cancer Stem Cells
CSR
Clinical Study Report
CT
Computed Tomography
CTCAE
Common Terminology Criteria for Adverse Events
CTLA 4
Cytotoxic T-lymphocyte–associated Antigen 4
DAR
Drug:mAb Ratio


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Abbreviation
Term
DCR
Disease Control Rate
DDI 
Direct Inhibition, Metabolism-Dependent Inhibition and 
Induction
DDI
Drug-Drug Interaction
DILI
Drug-induced Liver Injury
DLT
Dose Limiting Toxicities
DNA
Deoxyribonucleic Acid
DoR
Duration of Response
EC
Ethics Committee
ECG
Electrocardiograms
ECOG
Eastern Cooperative Oncology Group
EDP
Exposure During Pregnancy
EDTA
Ethylenediaminetetraacetic Acid 
EGFR
Epidermal Growth Factor Receptor
EI
Equivalence Interval
EPO
Erythropoietin
ER
Estrogen Receptor 
EU
European Union
EudraCT
European Clinical Trials database
FDA
Food and Drug Administration
FFPE
Formalin-Fixed Paraffin-Embedded
FIP
First In Patient
FSH 
Follicle Stimulating Hormone
G-CSF
Granulocyte Colony-Stimulating Factor
GGT
Gamma-glutamyl Transferase
GLP
Good Laboratory Practice
GMP
Good Manufacturing Practice
H&E
Hematoxylin and Eosin 
HBV
Hepatitis B Virus
hCG
Human chorionic Gonadotropin
HCV
Hepatitis C Virus
HIV
Human immunodeficiency Virus
HNSTD
Highest Non-Severely Toxic Dose
IB
Investigator Brochure
ICD
Immunogenic Cell Death
ICH
International Conference on Harmonisation
ID
Identification
IEC
Institutional Ethics Committee
IgG1
Immunoglobulin G1
IHC
Immunohistochemistry
IND
Investigational New Drug
INR
International Normalized Ratio
IOP
Intraocular Pressure


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Abbreviation
Term
IP
Intraperitoneal
IP Manual
Investigational Product Manual
irAE
Immune-related Adverse Events
irCR
Immune-related Complete Response
irPD
Immune-related Progressive Disease
irPR
Immune-related Partial Response
irSD
Immune-related Stable Disease
irRECIST
Immune-related Response Evaluation Criteria in Solid Tumors
IRB
Institutional Review Board
IUD
Intrauterine Device
IV
Intravenous
LFT
Liver Function Tests
LSLV
Last Subject Last Visit
mAb
Monoclonal Antibody
MCC
Merkel Cell Carcinoma
MedDRA
Medical Dictionary for Regulatory Activities
mg/kg
Milligram/kilogram
MHRA
Medicines and Healthcare products Regulatory Agency
MMAE
Monomethyl Auristatin E
MRI
Magnetic Resonance Imaging
MTD
Maximum Tolerated Dose
mTPI
Modified Toxicity Probability Interval
N/A
Not Applicable
Nab
Neutralizing Antibodies
NADPH
-Nicotinamide Adenine Dinucleotide Phosphate
NCCN
National Comprehensive Cancer Network
NCI
National Cancer Institute
NSAID
Nonsteroidal Anti-Inflammatory Drug
NSCLC
Non-Small Cell Lung Cancer
OR
Objective Response
ORR
Overall Response Rate
OS
Overall Survival
OVCA
Ovarian Cancer
PCD
Primary Completion Date
PD
Progressive Disease
PD
Pharmacodynamic
PD-1
Programmed Death 1
PD-L1
Programmed Death-Ligand 1
PDX
Patient Derived Xenograft
PE
Physical Exam
PI
Principal Investigator
PFS
Progression Free Survival
P-gp
P-glycoprotein


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Abbreviation
Term
PgR
Progesterone Receptor
PK
Pharmacokinetic
PO
By Mouth
PR
Partial Response
PR
Pulse Rate
PS 
Performance Scale
PT
Prothrombin Time
PTK7
Protein Tyrosine Kinase 7
Q2W
Once every 2 weeks
Q3W
Once every 3 weeks
QTcF
Fridericia QT Correction Formula
rCyp
Human Recombinant Cytochrome P450
RECIST
Response Evaluation Criteria in Solid Tumors
RNA
Ribonucleic Acid
RP2D
Recommended Phase 2 Dose
RR
Response Rate
RTK
Receptor Tyrosine Kinase
SAE
Serious Adverse Event
SAP
Statistical Analysis Plan
SD
Stable Disease
SOA
Schedule of Activities
SRSD
Single Reference Safety Document
STD10
Severely Toxic Dose for 10% of the animals
SUSAR
Suspected Unexpected Serious Adverse Reaction
t½ 
Terminal Half-Life
TBili
Total Bilirubin
TCR
T-cell receptor
TEAE
Treatment Emergent Adverse Event
TNBC
Triple Negative Breast Cancer
TTP
Time to Progression
UK
United Kingdom
ULN
Upper Limit of Normal
UPCR
Urine Protein to Creatinine Ratio
UPM 
Unit Probability Mass
USP
United States Pharmacopeia
US
United States
Vss
Volume of Distribution
WBC
White Blood Cell
WFI
Water for Injection
WHO
World Health Organization
18FDG-PET
Fluorine-18 Fluorodeoxyglucose Positron Emission 
Tomography


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


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


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


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


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Table 1. Objective Response Status at each Evaluation
Target Lesions
Non-target Disease
New Lesions
Objective status
CR
CR
No
CR
CR
Non-CR/Non-PD
No
PR
CR
Indeterminate or Missing
No
PR
PR
Non-CR/Non-PD, 
Indeterminate, or Missing
No
PR
SD
Non-CR/Non-PD, 
Indeterminate, or Missing
No
Stable
Indeterminate or 
Missing
Non-PD
No
Indeterminate
PD
Any
Yes or No
PD
Any
PD
Yes or No
PD
Any
Any
Yes
PD
Table 2. Objective Response Status at each Evaluation for Patients with Non-Target Disease Only
Non-target Disease
New Lesions
Objective status
CR
No
CR
Non-CR/Non-PD
No
Non-CR/Non-PD
Indeterminate
No
Indeterminate
Unequivocal progression
Yes or No
PD
Any
Yes
PD


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


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Appendix 4. National Cancer Institute (NCI) Common Terminology Criteria for 
Adverse Events (CTCAE)
The NCI CTCAE (Version 4.03 dated June 14, 2010) has been placed in the Study Manual 
for this protocol.  Alternatively, the NCI CTCAE may be reviewed on-line at the following 
NCI website: http://ctep.cancer.gov/reporting.ctc.html


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Appendix 5. Management of Infusion Related Reactions Including Allergic Reactions, 
Cytokine Release Syndrome or Anaphylaxis
In the event of infusion related reactions, Investigators should institute treatment measures 
according to best medical and nursing practice.
The following treatment guidelines should be employed:
If chills and fever occur, the infusion should be interrupted.  Patients may be treated 
symptomatically and the infusion should be restarted at 50% of the original rate.
NCI-CTCAE Grade 1 allergic reaction or cytokine release syndrome

Monitor for worsening condition.  If the reaction worsens, stop the infusion.  Institute 
premedication for subsequent infusions as per Section Administration.
NCI-CTCAE Grade 2 allergic reaction or cytokine release syndrome

Stop PF-06647020 infusion.

Administer bronchodilators, oxygen, acetaminophen, and others as medically 
indicated.

Resume infusion at 50% of previous rate once reaction has decreased to Grade 1 in 
severity.  Monitor closely for any worsening including respiratory status.  If the 
reaction recurs, stop infusion.  Institute premedication for subsequent infusions as per 
Section Administration.
NCI-CTCAE Grade 3 or Grade 4 allergic reaction or cytokine release syndrome or 
anaphylaxis

A Grade 3 anaphylaxis (hypersensitivity reaction) consists of symptomatic 
bronchospasm requiring parenteral medications with or without urticaria, 
allergy-related edema/angioedema, or hypotension.

A Grade 4 anaphylaxis (hypersensitivity reaction) is a life-threatening event requiring 
urgent intervention.
Treatment of Grade 3 or Grade 4 allergic reaction, cytokine release syndrome or 
anaphylaxis

Stop the PF-06647020 infusion immediately and disconnect infusion tubing from the 
patient.

Administer epinephrine, bronchodilators, antihistamines, glucocorticoids, intravenous 
fluids, vasopressor agents, oxygen, and others as medically indicated.


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
Monitor closely respiratory and cardiovascular status, be prepared for potential need 
for intubation.

Telephone Sponsor or designated representative to report an SAE as per 
Section Adverse Event Reporting.

For a NCI-CTCAE Grade 3 or 4 hypersensitivity reaction, study treatment will be 
discontinued.
Re-treatment following Grade 1 or Grade 2 allergic reactions or cytokine release 
syndrome

Once the PF-06647020 infusion rate has been decreased due to an allergic reaction or 
cytokine release syndrome, it will remain decreased for all subsequent infusions.

If the patient has a second reaction at the lower infusion rate, the infusion should be 
stopped and the patient should receive no further PF-06647020.

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-06647020.

If there are questions concerning whether an observed reaction is consistent with an 
allergic reaction, cytokine release syndrome, or anaphylaxis, the medical monitor 
should be contacted immediately to assist with grading the reaction.

PK, PD and ADA sampling should continue as long as the sampling does not 
interfere with the medical treatment of the patient.


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Appendix 6. Potent CYP3A Inhibitors and Inducers
Potent CYP3A Inhibitors
P-gp Inhibitor
Non-P-gp Inhibitor
elvitegravir/ritonavir (RIT)
indinavir or indinavir / RIT
lopinavir/RIT
nelfinavir
ritonavir
saquinavir or saquinavir / RIT
tipranavir/RIT
danoprevir/RIT
telaprevir
itraconazole
ketoconazole
clarithromycin
mibefradil
conivaptan
voriconazole
nefazodone
cobicistat
boceprevir
posaconazole
telithromycin
troleandomycin
List of medications from fda.gov and University of Washington Drug Interaction Database.  
Potent CYP3A inhibitors are defined as those drugs that increase the AUC of oral 
midazolam or other CYP3A substrates 5-fold
Potent CYP3A Inducers 
St. John’s Wort
avasimibe
carbamazepine 
phenytoin 
rifampin
List of medications from fda.gov. Potent 
CYP3A inducers are defined as those drugs 
that decrease the AUC of CYP3A substrates ≥ 
80%
As the list of CYP and/or P-gp inducers and inhibitors is a dynamic list continually changing 
when new information becomes available, use the following FDA website when deciding if a 
concomitant medication is considered a strong CYP3A/P-gp inhibitor and/or inducer: 
http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsL
abeling/ucm080499.htm
Selection of an alternate concomitant medication with no or minimal enzyme inhibition 
and/or induction potential is recommended.


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Appendix 7. Drug-Drug Interaction (DDI) Sub-Study
The objective of this DDI sub-study is to evaluate the effects of multiple-dose fluconazole, a 
moderate CYP3A4 inhibitor, on the pharmacokinetics of unconjugated payload 
(PF-06380101) following single-dose administration of ADC (PF-06647020).  Information 
on the effect of fluconazole on the PK profile of unconjugated payload (PF-06380101) will 
help better understand the risk of increase in exposure to PF-06380101 due to inhibition of 
the CYP3A4 mediated PF-06380101 elimination that may occur when moderate 
CYP3A4 inhibitors are present.
The potential effects of multiple-dose fluconazole on the PK of ADC (PF-06647020) and 
total antibody (hu6M024 mAb) will also be assessed.
Background:
The major cytochrome P450 isoform involved in the metabolism of unconjugated payload 
(PF-06380101) in humans was determined to be CYP3A4 (See Section 1.2.2 Nonclinical 
Pharmacokinetics). Physiologically-based PK modeling in SimCYP, utilizing nonclinical 
and preliminary clinical data, predicts an average 2 to 10-fold increase in 
PF-06380101 (payload) AUC with co-administration of ketoconazole, a potent 
CYP3A4 inhibitor, at a clinical dose (200 mg BID). Moderate CYP3A4 inhibitors, such as 
fluconazole, are predicted to have less impact on PF-06380101 AUC than ketoconazole, with 
average AUC increase estimated approximately 2-fold at clinical doses. The effect of 
fluconazole on PF-06380101 exposure cannot be precisely predicted at this time due to the 
lack of certainty surrounding the overall contribution of the CYP3A4 pathway to elimination 
of PF-06380101.
Fluconazole is a synthetic azole antifungal medication. In normal volunteers, the 
bioavailability of orally administered fluconazole is over 90% compared with intravenous 
administration. In fasted healthy volunteers, administration of a single oral 400 mg dose of 
fluconazole leads to a mean Cmax of 6.72 μg/mL which occurs between 1 and 2 hours, with a 
terminal plasma elimination half-life of approximately 30 hours after oral administration.  
Steady-state concentrations are reached within 5-10 days following oral doses of 50-400 mg 
given once daily. In general, a loading dose of twice the daily dose is recommended on the 
first day of therapy to result in plasma concentrations close to steady-state by the second day 
of therapy. The pharmacokinetics of fluconazole are markedly affected by reduction in renal 
function. Therefore, only patients with sufficient renal function (serum creatinine 
1.5 x upper limit of normal or creatinine clearance 60 ml/min) will be eligible for this 
sub-study. Data from a food effect study with fluconazole indicated that Cmax and AUC of 
fluconazole are not affected by food.  Therefore, fluconazole may be taken without regard to 
meals.
Fluconazole is a potent inhibitor of cytochrome P450 (CYP) isoenzyme 2C9 and 2C19, and a 
moderate inhibitor of CYP3A4. In normal volunteers, fluconazole is cleared primarily by 
renal excretion, with approximately 80% of the administered dose appearing in the urine as 
unchanged drug. About 11% of the dose is excreted in the urine as metabolites. Due to the 
majority of fluconazole being excreted unchanged in the urine, and due to the low observed 
concentrations (<0.05 ug/mL) of PF-06380101, PF-06380101 is not expected to impact the 
pharmacokinetics of fluconazole.


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Fluconazole has been associated with rare cases of serious hepatotoxicity, including liver 
failure and death.  If clinical signs and symptoms of liver disease develop, fluconazole 
treatment should be discontinued and liver function testing should be performed.  Please refer 
to the Fluconazole Package Insert for complete information on drug interactions, 
contraindications, warnings and precautions.
The first dose (C1D1) of PF-06647020 administered for the DDI sub-study will be 
2.8 mg/kg.  The second dose (C2D1) of PF-06647020 administered will be 1.4 mg/kg. An 
approximately 90% increase in unconjugated payload (PF-06380101) AUC is anticipated 
when co-administered with fluconazole (a loading dose of 400 mg followed by 200 mg daily 
doses).  The exposure of unconjugated payload (PF-06380101) following a single dose 
administration of 1.4 mg/kg of ADC (PF-06647020) with fluconazole is expected to be lower
than the unconjugated payload exposure previously observed at the 3.7 mg/kg using a 
Q3W schedule.
DDI Sub-Study Design:
This is an open-label, 2-period, fixed sequence study in patients to evaluate the effect of 
multiple-dose fluconazole on the PK of unconjugated payload (PF-06380101) following a 
single dose of ADC (PF-06647020). PF-06647020 will be administered on Day 1 in 21-day 
cycles. The DDI sub-study will also consist of two periods of intense PK sampling, Period A 
(Cycle 1) and Period B (Cycle 2). In the first period, Period A, a single-dose of 
PF-06647020 will be administered alone on C1D1 at 2.8 mg/kg. In Period B a single-dose of 
PF-06647020 will be administered on C2D1 at 1.4 mg/kg, in combination with fluconazole.
Fluconazole will be administered starting one day before Period B (C2D1). A maximum of 
10 patients will be enrolled to ensure at least 8 patients complete the DDI sub-study 
procedures. (See Schedule of Activities Table A1 and Table A2 for details). 
Enrollment of patients into the DDI sub-study will initially be carried out in a staggered 
manner. Once the first patient receives the second dose (C2D1) of PF-06647020 and has 
been evaluated for one week (C2D8) with no clinically significant treatment-related side 
effects requiring intervention or hospitalization, then a second patient may be enrolled.  
Remaining patients may be enrolled once the first and second patients have completed 
C2D8 with no clinically significant treatment-related side effects requiring intervention or 
hospitalization. 
Once completing Cycle 2, patients will continue to receive treatment with PF-06647020 at 
2.8 mg/kg every 21 days if the patient does not meet discontinuation criteria, as outlined in
Section 6.4. 
All study requirements and guidelines described in the main body of the protocol must be 
followed, in addition to any described in this Appendix 7.


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Patient Population:
This clinical trial can fulfill its objectives only if appropriate patients are enrolled.  The 
following eligibility criteria are designed to select patients for whom protocol treatment is 
considered appropriate.  All relevant medical and non-medical conditions and current 
medications should be taken into consideration when deciding whether this protocol is 
suitable for a particular patient. 
Inclusion Criteria:
Patient eligibility should be reviewed and documented by an appropriately qualified member 
of the investigator’s study team before patients are included in the study. 
Patients must meet all of the following inclusion criteria to be eligible for enrollment into the 
study:
1. Histological or cytological diagnosis of advanced/metastatic breast cancer, OVCA 
and NSCLC that is resistant to standard therapy or for which no standard therapy is 
available. 
2.
 
3. Age ≥18 years. 
4. ECOG Performance Status (PS) of 0 or 1. 
5. Life expectancy ≥12 weeks.
6. Adequate Bone Marrow Function as defined by:
a.
Absolute Neutrophil Count (ANC) ≥1,500/mm3 or ≥1.5 x 109/L;
b. Platelets ≥100,000/mm3 or ≥100 x 109/L;
c.
Hemoglobin ≥9 g/dL.
7. Adequate Renal Function as defined by:
a.
Serum creatinine ≤1.5 x upper limit of normal (ULN); or 
b. Estimated creatinine clearance ≥60 ml/min as calculated using the method 
standard for the institution. 
8. Adequate Liver Function as defined by:
CCI


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a.
Total serum bilirubin 1.5 x ULN unless the patient has documented Gilbert 
syndrome;
b. Aspartate and Alanine Aminotransferase (AST & ALT) 2.5 x ULN; 5.0 x ULN 
if there is liver involvement secondary to tumor; 
c.
Alkaline phosphatase 2.5 x ULN; (5 x ULN in case of bone metastasis). 
9. Recovery from all prior surgical or adjuvant treatment-related toxicities, to Baseline 
status, or a CTCAE Grade of 0 or 1, except for toxicities not considered a safety risk, 
such as alopecia.  Post-surgical pain will not be considered a basis for exclusion.
10. Negative serum/urine pregnancy test (for females of childbearing potential).
11. Male and female patients of childbearing potential must agree to use two highly 
effective method of contraception throughout the study and for at least 30 days after 
the last dose of assigned treatment.  A patient is of childbearing potential if, in the 
opinion of the investigator, he/she is biologically capable of having children and is 
sexually active.
12. Evidence of a signed and dated informed consent document indicating that the patient 
has been informed of all pertinent aspects of the study.
13. Willingness and ability to comply with the study scheduled visits, treatment plans, 
laboratory tests and other procedures. 
Exclusion Criteria:
Patients presenting with any of the following will not be included in the study: 
1. Patients with known symptomatic brain metastases requiring steroids Patients with 
previously diagnosed brain metastases are eligible if they have completed their 
treatment and have recovered from the acute effects of radiation therapy or surgery 
prior to the start of study medication, have discontinued corticosteroid treatment for 
these metastases for at least 4 weeks and are neurologically stable. 
2. Major surgery, radiation therapy or systemic anti-cancer therapy within 4 weeks of 
starting study treatment (6 weeks for mitomycin C or nitrosoureas).
3. Any condition affecting absorption of oral medications.
4. Prior treatment with a compound of the same mechanism.
5. Presence of Grade 2 peripheral neuropathy.


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6. Active and clinically significant bacterial, fungal or viral infection.  Known infections 
with hepatitis B (HBV), hepatitis C (HCV), known human immunodeficiency virus 
(HIV) or acquired immunodeficiency syndrome (AIDS)-related illness. 
7. Pregnant or breastfeeding; males and females of childbearing potential who are 
unwilling or unable to use two highly effective method of contraception as outlined in 
this protocol for the duration of the study and for at least 30 days after last dose of 
investigational product.
8. Currently active treatment in another clinical study.
9. Any of the following in the previous 12 months or currently: myocardial infarction, 
severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic 
congestive heart failure, cerebrovascular accident, transient ischemic attack or 
symptomatic pulmonary embolism, as well as ongoing cardiac dysrhythmias of 
NCI CTCAE Grade 2, atrial fibrillation of any grade, or QTc interval >470 msec at 
screening. 
10. Known or suspected hypersensitivity to recombinant human or murine proteins. 
11. Other severe acute or chronic medical or psychiatric condition, including recent 
(within the past year) or active suicidal ideation or behavior, or laboratory 
abnormality that may increase the risk associated with study participation or 
investigational product administration or may interfere with the interpretation of 
study results and, in the judgment of the investigator, would make the patient 
inappropriate for entry into this study.
12. Patients who are investigational site staff members directly involved in the conduct of 
the trial and their family members, site staff members otherwise supervised by the 
investigator, or patients who are Pfizer employees directly involved in the conduct of 
the trial.
13. Use of drugs or herbal supplements that are known CYP3A4 inhibitors (with 
exception of fluconazole doses specified in the protocol) within 7 days prior to the 
first dose of PF-06647020. The topical use of these medications (if applicable) may 
be allowed. Use of drugs or herbal supplements that are known CYP3A4 inducers 
within 12 days prior to the first dose of PF-06647020. 
14. Concurrent or anticipated use of drugs that are CYP3A4, CYP2C9 and/or 
CYP2C19 substrates with narrow therapeutic indices and/or known to prolong the QT 
interval, including but not limited to dihydroergotamine, ergotamine, pimozide, 
astemizole*, cisapride*, terfenadine*, paclitaxel, warfarin, phenytoin, 
S-mephenytoin, erythromycin, and quinidine (*withdrawn from U.S. market). 
15. Concurrent or anticipated use of hydrochlorothiazide or cimetidine. These 
medications may alter fluconazole exposure. 


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16. Patients with a history of hypersensitivity to fluconazole or its excipients or to other 
azole antifungals.
17. Patient having any contraindications to fluconazole administration according to the 
current package insert for fluconazole.
Treatment Administration:
ADC (PF-06647020):
PF-06647020 will be administered intravenously at a dose of 2.8 mg/kg on Cycle 
1 Day 1 (Period A) and at a dose of 1.4 mg/kg on Cycle 2 Day 1 (Period B). Patients 
experiencing toxicity may be managed with dose modification or discontinuation as outlined 
in Section 5.4.1 Recommended Dose Modifications. Patients will be allowed one dose 
reduction to 2.1 mg/kg. Patients requiring further dose reduction will be discontinued from 
the study.
See Section 5.4 Administration for further details regarding administration of PF-06647020.
Once a patient has completed Cycle 2, treatment with PF-06647020 will continue at the 
2.8 mg/kg dose if the patient does not meet discontinuation criteria, as outlined in
Section 6.4. 
Fluconazole: 
Administration of fluconazole will start with a loading dose of 400 mg by mouth (PO) on the 
morning of Cycle 1 Day 21. Patients will continue to take fluconazole in the morning at 
200 mg PO daily from Cycle 2 Day 1 through Cycle 2 Day 7.  On Cycle 2 Day 1 when 
fluconazole and PF-06647020 are to be co-administered, fluconazole should be taken 
approximately 1 hour before PF-06647020 administration. Fluconazole can be taken without 
regard to meals. 
On days of the scheduled site visits (Cycle 1 Day 21, Cycle 2 Days 1, 2, and 4), patients must 
take their daily dose of fluconazole at the clinic, under supervision of site staff.
Sites are to contact the Sponsor if there is any evidence of inappropriate administration of 
fluconazole, including delayed, missed, or multiple doses. Sponsor will use this information 
to determine if patient is evaluable for the DDI assessments.
Concomitant Medication:
In addition to Section 5.7 Concomitant Treatment(s) of the protocol, the following also 
applies for concomitant medications in this sub-study:


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Patients must not: (1) take any medications, herbal supplements or food known to be 
CYP3A4 inhibitors 7 days prior to the first dose of PF-06647020 until the completion of 
Cycle 2 Day 21; (2) take any medications, herbal supplements or food known to be 
CYP3A4 inducers 12 days prior to the first dose of PF-06647020 until the completion of 
Cycle 2 Day 21; (3) take any medications contraindicated with fluconazole while taking 
fluconazole and for 5 days after (Cycle 1 Day 21 through Cycle 2 Day 12) including 
dihydroergotamine, ergotamine, pimozide, astemizole, cisapride, terfenadine, paclitaxel, 
warfarin, phenytoin, S-mephenytoin, erythromycin, and quinidine; (4) take any medications 
which alter fluconazole exposure (including but not limited to hydrochlorothiazide and 
cimetidine) while taking fluconazole and for 5 days after (Cycle 1 Day 21 through Cycle 
2 Day 12).
Fluconazole is a potent inhibitor of cytochrome CYP2C9 and CYP2C19, and a moderate 
inhibitor of CYP3A4. Clinically or potentially significant drug interactions between 
fluconazole and the agents/classes provided in Table 14 have been observed or anticipated. 
In addition, there is a risk of increased plasma concentration of other compounds metabolized 
by CYP2C9, CYP2C19, and CYP3A4 co-administered with fluconazole. These elevated 
plasma concentrations may increase or prolong therapeutic and adverse effects of these 
drugs. Caution should be exercised when using any of these combinations. Whenever 
possible, plasma concentrations of these drugs should be monitored, and when appropriate, 
clinical monitoring for signs or symptoms of increased or prolonged pharmacologic effects is 
advised. The enzyme inhibiting effect of fluconazole persists 4–5 days after discontinuation 
of fluconazole treatment due to the long half-life of fluconazole.


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Table 14.
Drugs Which may Have Clinically Significant Drug Interactions When 
Administered With Fluconazole1
Alfentanil
Amitriptyline, nortriptyline
Amphotericin B
Astemizole2
Azithromycin
Calcium Channel Blockers
(ie, nifedipine, isradipine, 
amlodipine, verapamil, and felodipine)
Carbamazepine
Celecoxib
Cimetidine3
Cisapride2
Coumarin-type anticoagulants 
(ie, warfarin)
Cyclophosphamide
Cyclosporine
Erythromycin2
Fentanyl
Halofantrine
HMG-CoA reductase inhibitors
(ie, atorvastatin, simvastatin, fluvastatin)
Hydrochlorothiazide
Losartan
Methadone
Non-steroidal anti-inflammatory 
drugs (NSAIDs) (ie, ibuprofen, 
flurbiprofen, naproxen, 
lornoxicam, meloxicam, 
diclofenac)
Oral Contraceptives
Oral hypoglycemic (ie, glipizide, 
glyburide, tolbutamide)
Phenytoin
Pimozide2
Prednisone
Quinidine2
Rifabutin
Rifampin
Saquinavir
Short-acting benzodiazepines 
(ie, midazolam)
Sirolimus
Tacrolimus
Terfenadine2
Theophylline
Tofacitinib
Triazolam
Vinca Alkaloids
Vitamin A
Zidovudine
The enzyme inhibiting effect of fluconazole persists 4–5 days after discontinuation of fluconazole 
treatment due to the long half-life of fluconazole.
1.
This list is not all-inclusive.  From Diflucan® (fluconazole tablets) Package Insert Nov 2014. 
Please refer to package insert for description of drug interaction risk.
2.
Contraindicated with fluconazole. 
3.
Not permitted in this study, as it may decrease fluconazole exposure when given concomitantly.
This is not representative of other histamine-2 receptor antagonists.
Please refer to the Fluconazole Package Insert for complete information on drug interactions, 
contraindications, warnings and precautions.


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All concomitant medications for patients enrolling in this sub-study must be approved by the 
Sponsor.
Pharmacokinetic Assessment for PF-06647020, hu6M024 mAb and PF-06380101:
Blood samples for PK of unconjugated payload (PF-06380101), ADC (PF-06647020), and 
total antibody (hu6M024 mAb) will be collected as follows (also see Schedule of Activities 
Table A2 for details):
PK samples for determining concentrations of unconjugated payload (PF-06380101), ADC 
(PF-06647020), and total antibody (hu6M024 mAb) will be collected following 
PF-06647020 administration on Cycle 1 Day 1 during Period A (see Schedule of Activities 
Table A1 and Table A2 in Appendix 7).
PK samples for determining concentrations of unconjugated payload (PF-06380101), ADC 
(PF-06647020), and total antibody (hu6M024 mAb) will be collected after administration of 
PF-06647020 on Cycle 2 Day 1 during Period B (see Schedule of Activities Table A1 and 
Table A2 in Appendix 7).
Additional blood samples for PK evaluation should be collected if possible from patients 
experiencing unexpected or serious adverse events; with evidence of disease progression; or 
with other events where PK sampling is considered useful (upon agreement between 
investigator and sponsor). 
Pharmacokinetic Assessment for Fluconazole:
Blood samples for fluconazole will be collected as follows:
Pre-dose PK samples for fluconazole will be taken prior to fluconazole administration as per 
the Schedule of Activities (Table A1 and Table A2 in Appendix 7). Blood samples collected 
for fluconazole concentrations will only be analyzed if fluconazole concentration data are 
required for interpreting the PF-06380101 PK results. 
ECGs:
12-lead ECG will be collected as per the Schedule of Activities (Table A1 and Table A2 in 
Appendix 7) and should be performed after the patient has rested quietly for at least 
10 minutes. ECGs will be compared to the patient’s screening ECG and any clinically 
significant changes will be recorded as adverse events and evaluated further, as clinically 
warranted.  If the mean QTc is prolonged (value of >500 msec), the ECGs should be 
re-evaluated by a qualified person at the institution for confirmation.  Additional ECGs 
should be performed if clinically indicated.
If patient experiences cardiac or neurologic AEs (specifically syncope, dizziness, seizures, or 
stroke), an ECG (triplicate) should be obtained at the time of the event. 


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When matched with PK sampling, the ECG should be obtained before (preferable) or after 
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). For Cycle 2, 
Day 1, pre-dose PK sampling should occur prior to administration of fluconazole at the site, 
while the pre-dose ECG should be performed approximately 1 hour after fluconazole dose 
(~Tmax for fluconazole), prior to PF-06647020 infusion. 
Sample Size:
A maximum of 10 patients with advanced/metastatic solid tumor that is resistant to standard 
therapy or for which no standard therapy is available will be enrolled in this DDI sub-study 
to obtain 6 evaluable patients.  Evaluable patients are those that complete Period A 
(Cycle 1) and Period B (Cycle 2) with no evidence of missed doses of fluconazole.
See Section 9.3 for additional details regarding sample size.
Pharmacokinetic Data Analysis:
Serum concentrations of unconjugated payload (PF-06380101), ADC (PF-06647020), and 
total antibody (hu6M024 mAb) will be measured using validated method(s). 
Log-transformed Cmax and AUC values for unconjugated payload (PF-06380101) will be 
evaluated using a mixed-effect ANOVA model.  The ratios (Test/Reference) of geometric 
means and 90% confidence intervals for the ratios will be computed for AUC and Cmax to 
assess the interaction. ADC alone will be the Reference and ADC in the presence of 
fluconazole will be the Test.
A similar analysis will be conducted for ADC (PF-06647020) and total antibody 
(hu6M024 mAb), as supportive data.
Data from patients prematurely ending participation in the study or failing to meet evaluation 
criteria may be excluded from pharmacokinetic data evaluation.


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Table A1. SCHEDULE OF ACTIVITIES: DDI Sub-Study 
The schedule of activities table provides an overview of the protocol visits and procedures.  Refer to the Assessments section of the 
protocol for detailed information on each assessment required for compliance with the protocol. 
The investigator may schedule visits (unplanned visits) in addition to those listed on the schedule of activities, in order to conduct 
evaluations or assessments required to protect the well-being of the patient.
Visit Identifier
Screen/ 
Baseline1
(28 days)
Treatment Period
Post Treatment
Cycle 1 Only
(Days 1 to 21)
Cycle 2 and Subsequent 
Cycles
(Days 1 to 21)
Day 1
Day 4
(1)
Day 8
(1)
Day 15
(2)
Day 21 Day 1
(2)
Day 7
Day 8
(±2)
Day 15
(2)
End of 
Treatment29
(+7)
Follow Up30 (+7)
Informed Consent2
X
Tumor History3
X
Medical History4
X
Full Physical Examination5
X
X
X
Abbreviated Physical Examination
X
X
X
X
X
X
Ophthalmic Examination6
X
Baseline Signs and Symptoms7
X
Height
X
Weight8
X
X
X
Vital signs (BP/PR/Temp)9
X
X
X
X
X
X
X
X
X
X
ECOG Performance Status10
X
X
X
X
X
(12 lead) ECG11
X
X
X
X
X
X
Laboratory
Hematology12
X
X
X
X
X
X
X
X
X
Blood Chemistry13
X
X
X
X
X
X
X
X
X
Coagulation Panel14
X
X
X
Urinalysis15
X
X
X
X
Pregnancy test16
X
X
X
X
Registration and Treatment
Registration17
X
Study Treatment18
X
X
Fluconazole18
X
X
X


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Visit Identifier
Screen/ 
Baseline1
(≤28 days)
Treatment Period
Post Treatment
Cycle 1 Only
(Days 1 to 21)
Cycle 2 and Subsequent 
Cycles
(Days 1 to 21)
Day 1
Day 4
(±1)
Day 8
(±1)
Day 15
(±2)
Day 21 Day 1
(±2)
Day 7
Day 8
(±2)
Day 15
(±2)
End of 
Treatment29
(+7)
Follow Up30 (+7)
Tumor assessments 
CT or MRI scan or equivalent19
X
X (every 
6 weeks)
X
Other samplings 
 
 
CA125 Serum Biomarker (OVCA only)23
X
X(every 
6 weeks)
X
 
Blood Samples for PK25
See Pharmacokinetic, and Immunogenicity Sampling Schedule Table A2 below
Blood Sample for Immunogenicity Test 
(Anti-PF-06647020 Antibody)26
See Pharmacokinetic, and Immunogenicity Sampling Schedule Table A2 below
Other clinical assessments
Adverse Events27
X
X
X
X
X
X
X
X
X
X
Concomitant treatments and non-drug 
supportive interventions28
X
X
X
X
X
X
X
X
X
X
Abbreviations: CT = computed tomography; ECG = electrocardiogram; MRI =  magnetic resonance imaging; BP = blood pressure; PR = pulse rates; 
PK = pharmacokinetics; ECOG = Eastern Cooperative Oncology Group; OVCA = Ovarian cancer
Unless otherwise specified, laboratory values and assessments should be obtained prior to the PF-06647020 infusion.  If the infusion is held, assessments should 
still be performed.  For Cycle 2 and subsequent cycles, complete blood count (CBC), blood chemistry, other laboratory tests and brief physical examinations, 
values/assessments should be obtained within 72 hours (ideally within 24 hours) prior to the PF-06647020 infusion and key values should be received and 
reviewed to ensure appropriate values for dosing.
Footnotes
1.
Screening: To be conducted within 28 days prior to treatment start.
2.
Informed Consent: Must be obtained prior to undergoing any study specific procedures and may be >28 days from first dose.
3.
Tumor History: Will be collected within 28 days prior to treatment start.  Includes history of disease under study including details of primary diagnosis and 
treatment history. 
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4.
Medical History: Includes history of disease process other than the cancer under study (active or resolved) and concurrent illness. Includes prior treatments 
and any current medical treatments for any condition.
5.
Full Physical Exam: No need to repeat full physical exam on Cycle 1 Day 1 (C1D1) if baseline assessment performed within one week prior to that date. 
6.
Ophthalmic Examination: An eye exam (performed by an ophthalmologist) will be performed at screening. The eye exam includes Best Corrected Visual 
Acuity (BCVA), Intraocular Pressure (IOP) preferably by Goldmann applanation, Biomicroscopic Exam (also called slit lamp exam) to evaluate the 
Lids/Lashes/Adnexae, conjunctiva/sclera, cornea, anterior chamber, iris, lens, and Dilate fundus exam to evaluate the optic nerve, the vessels, the macula, 
and the peripheral retina. Further ophthalmic examinations should be guided by specific ocular signs and symptoms should they occur during treatment and 
follow up.
7.
Baseline Signs & Symptoms: On Day 1 prior to the start of study treatment, patients will be asked about any signs and symptoms experienced within the 
past 14 days of starting treatment.  Baseline signs and symptoms will be recorded on the Medical History Case Report Form (CRF) page.
8.
Weight: Will not be measured at each visit, however, patients should be monitored throughout the study for significant weight change.  If a patient’s weight 
fluctuates by more than 10% in either direction, weight should be collected to recalculate the appropriate dose for the next cycle.  In cases where individual 
institution/pharmacy require more frequent weight measurements, weight can be obtained on each day of administration, and the dose recalculated.
9.
Vital signs: Includes blood pressure (BP), temperature (oral, tympanic or axillary) and pulse rate (PR) to be recorded in the sitting position after 
approximately 5 minutes of rest.  On Day 1 of each cycle, vital signs should be measured prior to infusion start (pre-dose) and 1 hour after the start of the 
infusion.  Beginning at Cycle 8, the Day 8 assessments will be optional for patients that have achieved a CR, PR or SD if agreed upon by the treating 
physician.
10. Performance status: use Eastern Cooperative Oncology Group (ECOG) – see Appendix 3. 
11. 12 lead ECG (singlet): ECGs will be collected during Screening and at the End of Treatment visit.  Additional ECGs will be collected prior to dosing, at 
end of infusion and at Day 8 of each dose of study treatment.  When coinciding with blood sample draws for pharmacokinetics (PK), ECG assessment 
should be performed prior to blood sample collection, such that the blood sample is collected at the nominal time.  If the mean QTc is prolonged (value of 
>500 msec), the ECGs should be re-evaluated by a qualified person at the institution for confirmation.  Additional ECGs should be performed as clinically 
indicated.  Beginning at Cycle 8, the Day 8 assessments will be optional for patients that have achieved a CR, PR or SD if agreed upon by the treating 
physician.
12. Hematology: No need to repeat on C1D1 if baseline assessment performed within 72 hours prior to that date.  See Assessments section for Laboratory Tests 
list.  Beginning at Cycle 8, the Day 8 assessments will be optional for patients that have achieved a CR, PR or SD if agreed upon by the treating physician.
13. Blood Chemistry: No need to repeat on C1D1 if baseline assessment performed within 72 hours prior to that date.  See Assessments section for Laboratory 
Tests list.  Beginning at Cycle 8, the Day 8 assessments will be optional for patients that have achieved a CR, PR or SD if agreed upon by the treating 
physician.
14. Coagulation: See Assessments section for Laboratory Tests list.
15. Urinalysis: Dipstick or full urinalysis is acceptable.  Microscopic analyses if dipstick abnormal.  If 2+ protein on urine dipstick, then collect spot urine 
sample to calculate urine protein to creatinine ratio (UPCR).  See Assessments section for Laboratory Tests list.


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16. Serum/Urine Pregnancy Test: described in the Pregnancy Testing section.
17. Registration: Patient number and dose level allocation will be provided by Pfizer Inc.
18. Study Treatment: PF-06647020 will be administered once every 21 days as an IV infusion over approximately 60 minutes. 
19. Fluconazole Administration: 400 mg of fluconazole will be administered while the patient is in the clinic on Cycle 1 Day 21.  The remaining doses of 
fluconazole (200 mg) will be administered at the clinic on Cycle 2 Day 1 (1 hour before administration of PF-06647020) and on days when the patient 
returns for PK sampling (Cycle 2 Days 2 and 4). Fluconazole will be administered at the patient’s home on Cycle 2 Days 3, and 5 - 7.
20. Tumor Assessments: Tumor assessments will include all known or suspected disease sites and may include chest, abdomen and pelvis CT or MRI 
scans.  Brain scans and bone scans will be performed at baseline if disease is suspected and on-study as appropriate to follow disease.  Baseline central 
nervous system (CNS) imaging is not required with the exception of symptomatic patients to rule out CNS metastases.  CT or MRI scans are to be done 
every 6 weeks (±5 days) from the start of study treatment until disease progression by RECIST (v1.1) or death, or at the time of withdrawal from 
treatment (if not done in the previous 6 weeks).  The frequency may be reduced to every 12 weeks after 6 months of study treatment.  Tumor 
assessments should be fixed according to the calendar, regardless of treatment delays.  For patients enrolled in Part 2, responses of complete response (CR) 
or partial response (PR) must be confirmed by repeat assessment no less than 4 weeks after the criteria for response are first met.  Tumor assessments should 
be repeated at the End of Treatment visit if more than 6 weeks have passed since the last evaluation. Copies of all scans will be collected for potential 
central review. Additional information on diagnostic imaging procedures and collection will be included in the Imaging Manual.
 
 
 
 
  
 
23. CA125 Serum Biomarker: Ovarian cancer patients only.  Samples should be collected at pre-treatment, each tumor assessment (every 6 wks), and end of 
treatment.  Additional serum samples to be collected as per Investigator discretion.
 
25. PK Sampling: Specific timing for collection of serum pharmacokinetic samples can be found in the Pharmacokinetic, and Immunogenicity sampling 
schedule table below.
26. Immunogenicity Sample: Specific timing for collection of anti-PF-06647020 antibody samples can be found in the Pharmacokinetic, and Immunogenicity 
sampling schedule table below. 
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27. Adverse Event (AE) Assessments: Adverse events should be documented and recorded at each visit using National Cancer Institute Common Terminology 
Criteria for Adverse Events (NCI CTCAE) version 4.03.  The time period for actively eliciting and collecting AEs and SAEs (“active collection period”) for 
each patient begins from the time the patient provides informed consent through and including a minimum of 28 calendar days after the last investigational 
product administration.  If the patient begins a new anticancer therapy, the period for recording non-serious AEs on the CRF ends at the time the new 
treatment is started.  However, any SAEs occurring during the active collection period must still be reported to Pfizer Safety and recorded on the CRF, 
irrespective of any intervening treatment. Beginning at Cycle 8, the Day 8 assessments will be optional for patients that have achieved a CR, PR or SD if 
agreed upon by the treating physician.
28. Concomitant Treatments and Non Drug Supportive Interventions: All prior/concomitant medications within 28 days (4 weeks) prior to first dose of 
study treatment should be recorded in the CRF including supportive care drugs (eg, anti-emetic treatment and prophylaxis), and the drugs used to treat 
adverse events or chronic diseases, and non-drug supportive interventions (eg, transfusions).  Beginning at Cycle 8, the Day 8 assessments will be optional 
for patients that have achieved a CR, PR or SD if agreed upon by the treating physician.
29. End of treatment visit: Conducted at the visit that the patient is discontinued from the trial.  Assessments should be obtained if not completed in the last 
week.  Complete tumor assessments if not completed in the last 6 weeks. 
30. Follow up:  At least 28 days and no more than 35 days after end of treatment visit, patients will return to undergo review of concomitant medications, vital 
signs, and assessment for resolution of any treatment related toxicity.  Patients continuing to experience toxicity at this point following discontinuation of 
treatment will continue to be followed at least every 4 weeks until resolution or determination, in the clinical judgment of the Investigator, that no further 
improvement is expected.


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Table A2. PHARMACOKINETIC AND IMMUNOGENICITY SAMPLING SCHEDULE – DDI Sub-Study
Protocol Activity
Screen 
(28 days)
Treatment Period
Cycle 1 (Period A) and Cycle 4
Cycle 2 (Period B)
Cycles 3, 5 and 
Every Cycle 
Thereafter
EOT
Day 1
Day 2 Day 4 Day 8 Day 
15
Day 
21
Day 1
Day 2 Day 4 Day 8 Day 
15
Day 1
Pre-dose*
1 hr*
4 hr*
24
hr*
Pre-dose* 0 hr 1 hr* 4 hr*
24
hr*
Pre-dose* 1 hr*
Blood Samples for 
PF-063801011
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Blood Samples for 
PF-06647020 and 
hu6M024 mAb2
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Blood Sample for Fluconazole3
X
X
X
X
X
Blood Sample for 
Immunogenicity Test 
(Anti-PF-06647020 Antibody)4
X
X
X
X
X
* Sampling times are in relation to the start of the most recent infusion; 1 hr samples should be collected immediately before the infusion ends. All samples obtained within 
10% of the nominal time (eg, within 6 minutes of a 60 minute sample) will be considered protocol compliant, and the exact time of the sample collection will always be noted on 
the CRF.
1.
Blood PK sample for PF-06380101: 4 mL of whole blood will be collected for PK analysis of unconjugated payload (PF-06380101).
2.
Blood PK sample for PF-06647020 and hu6M024 mAb: 6 mL of whole blood will be collected for PK analysis of ADC (PF-06647020) and total antibody 
(hu6M024 mAb).
3.
Blood PK sample for fluconazole: Cycles 1 and 2 only.  Pre-dose samples (within 3 hr of the next scheduled dose of fluconazole) will be collected and actual sample 
collection times will be recorded. The fluconazole PK samples will not be analyzed unless required for interpreting the PF-06380101 PK results.
4.
Blood sample for immunogenicity test: Blood samples (6 mL) for immunogenicity testing against PF-06647020 will be collected. Collection of serum to detect the 
presence of antibodies to PF-06647020 is to be obtained prior to the start of treatment.  Patients having an unresolved adverse event that is possibly related to 
anti-PF-06647020 antibodies at their last assessment will be asked to return to the clinic for ADA and drug concentration blood sampling at approximately 3 month intervals 
until the adverse event or its sequelae resolve or stabilize at a level acceptable to the investigator and sponsor.


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Appendix 8. Q2W Regimen Expansion Sub-Study (Single Agent PF-06647020 and 
Combination of PF-06647020 with Avelumab in patients with OVCA and NSCLC)
A1. Background and Rationale
This sub-study will evaluate the safety, PK, and anti-tumor activity of single agent 
PF-06647020 and combination of PF-0664720 with avelumab when administered Q2W in 
patients with platinum-refractory or resistant OVCA and patients with recurrent advanced 
NSCLC.  
This sub-study contains a dose escalation (Part 1) and a dose expansion (Part 2).  The Part 1 
will be conducted in patients with platinum resistant or refractory OVCA and patients with 
recurrent advanced NSCLC; and PF-06647020 will be administered Q2W as a single agent 
treatment.  After a favorable safety profile and preliminary anti-tumor activity as a single 
treatment of PF-06647020 in Part 1 is observed, the Part 2 dose expansion will be started to 
further investigate safety, PK and efficacy of Q2W PF-06647020 in at least three cohorts of 
patients: 

Cohort 1 PF-06647020 as a single agent treatment in patients with platinum resistant 
or refractory OVCA.

Cohort 2 PF-06647020 as a single agent treatment in patients with recurrent advanced 
NSCLC.

Cohort 3 PF-06647020 in combination with avelumab in platinum resistant or 
refractory OVCA.  
If supported by safety and anti-tumor activity, additional cohort with approximately 
24 patients with recurrent advanced NSCLC may be considered in Part 2 to receive 
combination of PF-06647020 with avelumab.


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The study scheme for the Q2W regimen expansion is described in the diagram below: 
A1.1. PF-06647020
PF-06647020, a novel ADC targeting PTK7, has been investigated in 112 patients (as of 
17 March 2017) with advanced cancers including platinum and/or paclitaxel heavily 
pre-treated OVCA. In the ongoing Phase I study, as of 17 March 2017, total of 112 patients 
with heavily pre-treated cancers have been treated with PF-06647020 on a Q3W regimen at 
different dose levels in the ongoing Phase I study, of which 44 were OVCA patients, 25 were 
NSCLC patients, and 31 were TNBC patients, 12 patients had other types of solid tumor.
Of the total 44 OVCA patients who received PF-06647020 treatment, 42 were treated at 
2.8 mg/kg, 1 at 2.1 mg/kg, and 1 at 3.7 mg/kg.  In 38 patients who were considered evaluable 
for ORR assessment, 9 patients achieved objective response (1 CR, and 8 PR) with an ORR 
of 24% (95% CI, 13%, 39%) and 18 patients (47%) had a best response with SD. Median 
PFS was 12.6 weeks (95% CI, 12, 24). Median duration of treatment with PF-06647020 was 
8.1 weeks (range 0.1-45.3 weeks).
Of the total 25 NSCLC patients received PF-06647020 treatment, 22 were treated at 
2.8 mg/kg, 2 at 1.25 mg/kg, 1 at 2.1 mg/kg. In 23 patients who were considered evaluable 
for ORR assessment, 4 patients achieved PR with an ORR of 17% (95% CI, 7%, 37%) and 
9 patients (39%) had a best response with SD. Median PFS was 18.1 weeks (95% CI, 
6, 30.1) and median duration of treatment with PF-06647020 was 9.0 weeks 
(range-0.1-46.3-weeks).
Of the total 31 TNBC patients received PF-06647020 treatment, 27 were treated at 
2.8 mg/kg, 2 at 2.1 mg/kg, 2 at 3.7 mg/kg.  In 27 patients who were considered evaluable for 
ORR assessment, 6 achieved PR with an ORR of 22% (95% CI, 11%, 41%). Eight (30%) 
patients had a best response of SD.  Median PFS was 8.3 weeks (95% CI, 6, 23.6) and a 
median duration of treatment with PF-06647020 was 3.0 weeks (range 0.1-40.3 weeks). 


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The most frequently observed PF-06647020 treatment related AEs were nausea, alopecia, 
fatigue, headache, vomiting, and arthralgia, most were Grade 1 or 2.  A total of 15 patients 
(35.7%) experienced a Grade 3 treatment-related AE, most common was neutropenia 
(10 patients, 23.8%), headache, myalgia, vomiting, and hypomagnesaemia (2 patients (4.8%)
each).
When administered Q3W, PF-06647020 at RP2D 2.8 mg/kg demonstrated encouraging 
anti-tumor activity with a generally well acceptable safety profile. Preliminary PK analyses 
and simulation suggest that Q2W dosing is expected to be better aligned with PK 
characteristics of PF-06647020, with lower peak-to-trough PK fluctuation compared to the 
Q3W regimen.  Therefore the Q2W regimen of PF-06647020 would result in an increased 
exposure while maintaining a tolerable safety profile.  
Several lines of evidence suggest that combining the PTK7-targeted ADC with avelumab 
would improve clinical outcomes.  In preclinical studies, combination of avelumab with 
chemotherapies showed improved anti-tumor activity.20  A recent preclinical study 
demonstrated that immunotherapy can be enhanced by localized chemotherapy but not 
systemic chemotherapy;21 indeed the PTK7-targeted ADC delivers a potent chemotherapy 
preferentially to the tumor cells and thus is distinguished from standard chemotherapies.  In 
addition, the PTK7-targeted ADC could stimulate anti-tumor immunity (and thus stimulate 
the response to avelumab) by multiple mechanisms: (1) auristatins can activate dendritic cells 
(Pfizer, unpublished data), and the expression of PTK7 on dendritic cells could increase the 
delivery of auristatin to those cells; (2) anti-angiogenic activity can promote immune cell 
infiltration into tumors, and the PTK7-targeted ADC specifically inhibits angiogenesis; 
(3) immunogenic cell death can stimulate anti-tumor immunity, and auristatins induce this 
phenotype in cancer cell lines.19
A1.2. Avelumab (MSB0010718C)
Avelumab (MSB0010718C), a fully human antibody of the IgG1 isotype, specifically targets 
and blocks PD-L1, the ligand for PD-1 receptor.  This interaction inhibits the suppressive 
effects of PD-L1 on CD8 positive T cells, and thus restores the cytotoxic T cell response 
against the tumor.  In preclinical studies, combination of avelumab with chemotherapies 
showed improved anti-tumor activity.20 Broad expression of PD-L1 was observed in ovarian 
cancer samples, and higher expression of PD-L1 was associated with significantly worse 
prognosis.32 Preliminary data from the ongoing OVCA Study EMR 100070-001, which is 
being conducted by Merck KGaA/EMD Serono (EudraCT number 2013-002834-19, 
NCT01772004) showed an overall response rate (ORR) of 10.7% (8/75) and stable disease 
(SD) in an additional 44% (33/75) of patients with advanced OVCA.  
For complete details of the in vitro and nonclinical studies, refer to avelumab Investigator’s 
Brochure (IB).20


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A1.2.1. Avelumab Safety (MSB0010718C)
As of 15 February 2015, 1300 patients had been treated in pooled expansion cohorts of 
patients with advanced cancers.  Of the 1300 patients treated, 621 (47.8%) experienced at 
least 1 Grade 3 TEAE, and 813 (62.5%) had treatment-related TEAEs, of whom 124 (9.5%) 
had Grade 3 treatment-related TEAEs.
The most frequently reported (incidence 10% in the pooled expansion cohort) TEAEs (any 
grade) in the pooled expansion cohort are summarized in Table 15.  The most frequently 
reported (occurring in at least 5 patients in the pooled extension cohort) Grade 3 
treatment-related TEAEs in the pooled expansion cohort are presented in Table 16.
Table 15.
Most Frequently Reported (Incidence 10% in the Pooled Expansion 
Cohort) Treatment-Emergent Adverse Events (TEAEs) in the Pooled 
Expansion Cohort (Any Grade)
MedDRA PT
Pooled Expansion Cohort Patients (n=1300)
n (%)
Number of patients with at least 1 TEAE
1200 (92.3)
Fatigue
356 (27.4)
Nausea
276 (21.2)
Infusion-related reaction
211 (16.2)
Diarrhea
205 (15.8)
Constipation
204 (15.7)
Decreased appetite
194 (14.9)
Vomiting
188 (14.5)
Weight decreased
159 (12.2)  
Abdominal pain
156 (12.0)
Anemia
155 (11.9)
Cough
152 (11.7)
Dyspnea
148 (11.4)
Pyrexia
148 (11.4)
Chills
137 (10.5)
Source: Avelumab Investigator’s Brochure Version 5 Table 15
Table 16.
Most Frequently Reported (in 5 Patients in the Pooled Expansion Cohort) 
Grade 3 Treatment-Related TEAEs in the Pooled Expansion Cohort
MedDRA PT
Pooled Expansion Cohort Patients (n=1300)
n (%)
Number of patients with at least 1 TEAE
124 (9.5)
Gamma-glutamyl transferase increased
9 (0.7)
Infusion-related reaction
9 (0.7)
Fatigue
8 (0.6)
Lipase increased
8 (0.6)
Anemia
7 (0.5)
Dyspnea
6 (0.5)
Aspartate aminotransferase increased
5 (0.4)
Source: Avelumab Investigator’s Brochure Version 5 Table 17


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As of 05 November 2015, 509 of 1300 patients (39.2%) in the pooled expansion cohort had 
at least 1 serious TEAE. Treatment-related serious TEAEs were reported in 71 of the 
1300 patients (5.5%) in the pooled expansion cohort.  These included infusion-related 
reaction (11 patients; 0.8%), pneumonitis (8 patients; 0.6%), pyrexia and dyspnea (each in 
5 patients; 0.4%), autoimmune hepatitis (3 patients; 0.2%), and asthenia, blood creatine 
phosphokinase increased, abdominal pain, colitis, diarrhea, vomiting, hyponatremia, adrenal 
insufficiency, and non-cardiac chest pain (each in 2 patients; 0.2%). All other 
treatment-related TEAEs were reported in a single subject (0.1%) only.
As of 05 November 2015, 466 deaths (35.8%) occurred in the dose expansion cohorts.  The 
majority of deaths in the dose expansion cohorts were due to progressive disease 
(360 patients; 27.7%).  Overall, a total of 5 deaths (0.4%) due to TEAEs related to trial 
treatment were considered as primary reason of the death by the investigator. Two additional 
cases of death were reported and assessed as treatment-related, but the treatment related 
TEAEs were not considered as the primary reason of death. A total of 142 deaths (10.9%) 
occurred within 30 days patients of last treatment in the dose expansion cohorts.  Overall 
there were (14%) patients who experienced treatment related AEs with fatal outcome; in 
4 patients the treatment-related AE was reported as the primary cause of death as noted 
above.  These 7 cases with AEs related to study treatment included: pneumonitis radiation 
induced and dyspnea; acute liver failure associated with autoimmune hepatitis (no 
biopsy/autopsy performed); disease progression; fatal anoxic brain injury after cardiac arrest; 
autoimmune hepatitis with hepatic failure and fatigue (no biopsy/autopsy performed); 
respiratory distress and sepsis; and acute respiratory failure, acute exacerbation chronic 
obstructive pulmonary disease (COPD), and leukocytosis (occurred after the end of the 
on-treatment period).
As of 05 November 2015, a total of 175 patients (13.5%) treated in the dose expansion 
cohorts withdrew permanently from trial treatment due to one or more TEAE.  Of these 
patients with treatment discontinuations, 79 patients (6.1%) in the dose expansion cohorts 
had treatment discontinuations that were due to treatment-related TEAEs.  These TEAEs 
were infusion-related reaction (25 withdrawals; 1.9%), Gamma glutamyl transferase (GGT) 
increased and rash (5 withdrawals each, 0.4%), and aspartate aminotransferase increased, 
blood creatine phosphokinase increased, and lipase increased (3 patients each, 0.2%), and 
ALT increase, autoimmune hepatitis, and dyspnea (2 patients each, 0.2%).  All other 
treatment-related TEAEs leading to treatment discontinuation were observed in a single 
patient (0.1%) only.  
 
 
 
 
 
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Infusion-Related Reactions: Two unexpected serious adverse reactions (SUSARs); 
anaphylactic reaction and infusion-related reaction) involving 2 patients were reported in 
December 2013 and triggered a cumulative review of serious and non-serious cases of 
infusion-related reactions/hypersensitivity across the avelumab program.  Following 
evaluation of safety signals, infusion-related reactions/hypersensitivity have been classified 
as a newly identified risk (previously classified as a potential risk) and a mandatory 
premedication regimen of a histamine H1 receptor (H1) blocker plus acetaminophen was 
implemented for all trial patients starting 29 January 2014.
Starting from 29 January 2014, a mandatory premedication with H1 blockers plus 
acetaminophen was implemented for all patients who are to receive avelumab.  One hundred 
and ninety-four of 1259 patients (15.4%) in the pooled treatment expansion cohort 
experienced infusion-related reaction in the presence of premedication with 50 patients 
(4.0%) having Grade 1, 138 patients (11.0%) having Grade 2, 4 patients (0.3%) having 
Grade 3, and 2 patients (0.2%) having Grade 4 events.  Two patients (5.3%) in the dose 
escalation cohort reported infusion-related reactions (both Grade 2) in the presence of 
premedication. In addition to the aforementioned patients, one case of Grade 4 cardiac arrest 
occurred 1.5 hours after the third infusion of avelumab (10 mg/kg).  The patient died due to 
an anoxic brain injury 7 days later; no autopsy was performed. 
Guidelines for the management of infusion-related reactions and severe hypersensitivity 
reaction are found in Section A7.3.3.2.  A complete guideline for the emergency treatment of 
anaphylactic reactions according to the Working Group of the Resuscitation Council (United 
Kingdom) and can be found at 
https://www.resus.org.uk/pages/reaction.pdfhttps://www.resus.org.uk/pages/reaction.pdfhttps
://www.resus.org.uk/pages/reaction.pdf.
Additional information for this compound may be found in the SRSD, which for this study is 
the Investigator Brochure.20
A1.2.2. Avelumab Pharmacokinetics (MSB0010718C)
PK following the first 1-hour infusion and dose proportionality of avelumab have been 
characterized in 77 mainly Caucasian patients treated in the dose escalation and expansion 
cohorts of the Phase 1 Study EMR 100070-001 by standard non-compartmental analysis.  
This analysis revealed that the exposure parameters of Cmax and AUC after the first dose 
generally increased in an approximately dose-proportional manner in the dose range between 
3 to 20 mg/kg.  Apparent half-life tended to increase with dose, likely due to target mediated 
disposition at lower doses, but terminal half-life at 10 and 20 mg/kg doses were similar 
(102-120 hours).  This likely indicates that target mediated elimination does not increase at 
these two doses and target occupancy is very high. 
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A1.2.3. Efficacy and Safety in OVCA Patients treated with Avelumab (MSB0010718C)
Single-agent avelumab activity at 10 mg/kg Q2W was evaluated in heavily pre-treated 
epithelial ovarian cancer patients in an ovarian-specific expansion cohort in Study 
EMR100070-001.  Patients with OVCA whose disease progressed on standard therapy were 
eligible.  124 patients were treated as of 23 October 2015.  Median age was 62 years (range 
27-84 years); ECOG performance status was 0 (48%) or 1 (52%); median number of prior 
therapies for locally advanced or metastatic disease (excluding adjuvant treatment) was 
3 (range, 1-10).  Median duration of treatment with avelumab was 12 weeks 
(range 2-54 weeks), and 17 patients remained on treatment.  Twelve patients (9.7%, 95% CI, 
5.1%, 16.3%) achieved an unconfirmed best objective response (BOR) of partial response 
(PR).  Six out of 12 responses were ongoing at the time of data cutoff.  Fifty-five (44.4%) 
patients had stable disease.  Two additional patients had partial response by immune-related 
response criteria.  Median progression-free survival was 11.3 weeks.
Avelumab was well-tolerated in the OVCA expansion cohort.  Table 17 demonstrates 
treatment-related AEs observed in 5% of patients as of 13 February 2015 (n=75).  The 
following Grade 3 avelumab-related AEs were observed in a total of 6 patients (8.0%):  one 
event each of peripheral edema, localized edema, increased lipase, increased blood creatine 
phosphokinase, arthritis, myositis, hyperglycemia, anemia, tumor pain.  There were no 
Grade 4 or 5 AEs related to avelumab reported in this cohort.  Related serious TEAEs were 
observed in 3 patients (4.0%): Dyspnea (1), pyrexia (1), non-cardiac chest pain (1),
flushing (1), localized edema (1), and peripheral edema (1).  Immune-related TEAEs were 
seen in 8 patients (10.7%) and included hypothyroidism (5; 6.7%), arthritis (2; 2.7%), and 
myositis (1; 1.3%).  No drug-related intestinal obstruction or perforations occurred.  
Discontinuation related to treatment with avelumab was reported in 9 patients (12.0%) 
[Pfizer/Merck KGaA data on file, cutoff 13 February 2015].20
Table 17.
Avelumab Treatment Related Adverse Events (Incidence 5%) in the 
OVCA Cohort
Events (n=75)
Treatment-Related AEs, all grades*, n (%)
Any event
52 (69.3)
Fatigue
12 (16.0)
Chills
9 (12.0)
Nausea
8 (10.7)
Diarrhea
8 (10.7)
Infusion-related reaction
6 (8.0)
Rash
6 (8.0)
Vomiting
4 (5.3)
Constipation
4 (5.3)
Hypothyroidism
4 (5.3)
Source: Table 15.3.1.5C.
Complete information for avelumab may be found in the SRSD, which for this study is the 
avelumab Investigator’s Brochure.20


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A1.3. Summary of Benefit/Risk Assessment
An evaluation of the anticipated benefits and risks as required in Article 3(2)(a) of Directive 
2001/20/EC (cf. Article 6(3)(b) of Directive 2001/20/EC) has been conducted.
PF-06647020 as a single agent treatment with Q3W regimen in the Phase I study has 
demonstrated encouraging anti-tumor activity in heavily pre-treated patients with advanced 
solid tumors including OVCA, NSCLC and TNBC with ORR ranging from 17-24%.  The 
median PFS (8-18 weeks) observed is within the expected range and continues to evolving 
due to the nature of the ongoing study. 
AE and laboratory test data for PF-06647020, as of 17 March 2017, suggested PF-06647020, 
administered at Q3W, is generally well tolerated and has an acceptable and manageable 
safety profile.  The AEs observed were in line with those expected in patients with advanced 
solid tumors treated by an ADC.  Febrile neutropenia and neutropenia observed in the study 
are considered manageable toxicities with appropriate prophylaxis and/or clinical 
management but remain classified as potential safety concerns.  Grade 3 headache and 
fatigue were identified as DLTs in the dose escalation study and were well managed with 
dose reduction and/or treatment following institutional guidance.  Preliminary 
exposure-response analysis revealed an apparent correlation between PF-06647020 PK 
exposure and ORR in OVCA patients; sustained PF-06647020 PK exposure appeared to be 
associated with higher ORR.  A Q2W dosing regimen is predicted to be better aligned with 
PK characteristics of PF-06647020, with lower peak-to-trough PK fluctuation compared to 
the Q3W regimen.  Therefore the Q2W regimen of PF-06647020 would result in an 
increased PK exposure while maintaining a tolerable safety profile.  A mitigation plan 
including prophylaxis of anti-emetics and supplement of growth factors as needed, and 
guideline for dose reduction or treatment discontinuation have been implemented in the 
ongoing Phase I dose expansion portion of the study and will be utilized in this Q2W 
regimen expansion study.  
Available AE and laboratory abnormality data from patients with advanced solid tumors
treated with single-agent avelumab suggest an acceptable safety profile of the compound.  
Most of the observed events were either in line with those expected in patients with advanced 
solid tumors or with similar class effects of monoclonal antibodies blocking the PD-1/PD-L1 
axis.  Infusion-related reactions including hypersensitivity and irAEs/autoimmune disorders 
have been identified as important risks for avelumab.  Respective risk mitigation measures 
have been implemented in all ongoing clinical studies with avelumab, including this clinical 
trial protocol.  These mitigation measures include a treatment algorithm and guidelines for 
treatment interruption and discontinuation in case of irAEs, as well as mandatory 
pre-treatment with a histamine H1 receptor (H1) blocker and acetaminophen.  Avelumab 
demonstrated clinical activity in heavily pretreated OVCA patients in an expansion cohort of 
an ongoing Phase 1 study and is being evaluated in ongoing Phase 3 trials as a single agent or 
in combination with standard of care treatment in multiple types of advanced cancers 
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Thus, the projected benefit/risk of PF-06647020 given as a single agent treatment or in 
combination with avelumab at a Q2W regimen is anticipated to be favorable for investigation 
inan advanced cancer patient population.
A2. STARTING DOSE RATIONALE FOR Q2W REGIMEN
A2.1. PF-06647020 
The recommended starting PF-06647020 dose for the Q2W regimen study will be 2.1 mg/kg,
administered as 1-hour IV infusions.  
In the ongoing trial, single agent PF-06647020 at doses ranging from 0.2 mg/kg to 3.7 mg/kg
Q3W were evaluated in 112 patients with advanced solid tumors including 44 patients with 
heavily pre-treated OVCA.  PF-06647020 was found to be generally well tolerated with an 
acceptable safety profile.  The RP2D of PF-06647020 was identified as 2.8 mg/kg Q3W, 
which was used in the ongoing dose expansion studies including TNBC, OVCA and NSCLC 
and has been demonstrated with encouraging anti-tumor clinical activity. 
Preliminary exposure-response analysis revealed an apparent correlation between 
PF-06647020 exposure and ORR in OVCA patients; sustained PF-06647020 PK exposure 
appeared to be associated with higher ORR.  Preliminary PK analysis suggested that Q2W 
schedule would be better aligned with the PK characteristics of PF-06647020, resulting in 
lower peak-to-trough PK fluctuation, compared to Q3W, likely yielding a higher exposure 
while maintaining a tolerable safety profile. The recommended starting dose of 2.1 mg/kg 
for Q2W dosing represents 75% of the MTD of 2.8 mg/kg determined for PF-06647020
Q3W.  PK simulations suggests that the cumulative exposure of 6 weeks of the 2.1 mg/kg 
Q2W is expected to be generally comparable to that of the 2.8 mg/kg Q3W, with a slightly 
lower Cmax, and expected to be tolerable.   
A2.2. Avelumab 
To date, avelumab has been administered at the clinically active, safe and tolerable dose of 
10 mg/kg Q2W to more than 1700 patients across multiple indications.  Furthermore, this 
10 mg/kg Q2W avelumab dosing regimen has been approved by the US Food and Drug 
Administration (FDA) as the first treatment for Merkel Cell Carcinoma (MCC).  It has also 
recently been approved at this dose and regimen as a second line treatment of Urothelial 
Carcinoma.  Avelumab was originally dosed on a mg/kg basis in order to reduce inter-subject 
variability in drug exposure. However, emerging data for monoclonal antibodies, including 
marketed PD-1 and PD-L1 immune checkpoint inhibitors nivolumab, pembrolizumab and 
atezolizumab, reveal that body weight-based dosing regimens do not result in less variability 
in measures of exposure over fixed (ie, body-weight independent) dosing regimens).29,30,31
Additionally, fixed dosing offers the advantages of less potential for dispensing errors, 
shorter dose preparation times, and greater ease of administration.
Population PK analysis was conducted based on the acquired PK data across three 
single-agent avelumab studies in patients with 14 different types of cancer. PK simulations 
suggest that exposures to avelumab across the available range of body weights are similar 


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with 800 mg Q2W compared to 10 mg/kg Q2W. Low-weight subjects tended towards 
marginally lower exposures relative to the rest of the population when weight-based dosing 
was used, and marginally higher exposures when fixed dosing was applied. However, the 
implications of these exposure differences are not expected to be clinically meaningful. 
Furthermore, the 800 mg Q2W dosing regimen is expected to result in Ctrough >1 μg/mL 
required to maintain avelumab serum concentrations at >90% Target Occupancy (TO) 
throughout the entire dosing interval in all weight categories.
Therefore, in this clinical trial, a fixed dosing regimen of 800 mg administered as a 1-hour IV 
infusion Q2W will be utilized for avelumab.  
A3. OBJECTIVES AND ENDPOINTS FOR Q2W REGIMEN
A3.1. Objectives
Primary Objectives
•
Part 1: To assess safety and tolerability at increasing dose levels of PF-06647020
administered intravenously as a single agent on a Q2W dosing schedule.
•
Part 1: To determine the MTD and select the RP2D of PF-06647020 as a single agent 
treatment on a Q2W dosing schedule.
•
Part 2: To evaluate the overall safety profile of PF-06647020 as a single agent and in 
combination with avelumab at Q2W dosing schedule in OVCA and NSCLC patients 
at the RP2D.
Secondary Objectives 
•
To characterize the single and multiple dose PK of ADC (PF-06647020), total 
antibody (hu6M024 mAb) and unconjugated payload (PF-06380101) when 
PF-06647020 administered alone or on combination with avelumab, and PK of 
avelumab.
•
To evaluate the immunogenicity as measured by presence of ADA in patients treated 
with PF-06647020 or PF-06647020 in combination of avelumab.
•
To evaluate anti-tumor activity of PF-06647020 as a single agent and when given in 
combination with avelumab in patients with OVCA and NSCLC.
 
 
 
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A3.2. Study Endpoints 
Primary Endpoints
•
Part 1: First Cycle DLTs for the dose escalation portion.  A cycle is 28 days in 
duration.
•
Part 2: AEs (as graded by NCI CTCAE v.4.03); laboratory abnormalities (as graded 
by NCI CTCAE v.4.03); vital signs (blood pressure, pulse rate); or ECGs.
Secondary Endpoints
•
Pharmacokinetics: PK parameters of PF-06647020, total antibody (hu6M024 mAb),
unconjugated payload (PF-06380101), and avelumab.  
•
Immunogenicity: Incidence of ADA and Nab against PF-06647020 and avelumab.
•
Efficacy: OR, DoR, DCR, TTP, and PFS, as determined by Investigator [As assessed 
by RECIST version 1.1] (Appendix 2).
 
 
 
 
 
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A4. STUDY DESIGN FOR THE Q2W REGIMEN EXPANSION  
The expansion is designed to evaluate safety, PK and anti-tumor efficacy of a Q2W dosing 
schedule as a single agent treatment in patients with OVCA and NSCLC, and combined 
treatment of PF-06647020 with avelumab in OVCA patients.  If supported by safety and 
anti-tumor efficacy, additional combination study of PF-06647020 with avelumab may also 
be investigated in approximately 24 patients with NSCLC.  
The study contains two parts, a Part 1 dose escalation and Part 2 dose expansion.  Part 1 
contains a dose escalation scheme to estimate the MTD/RP2D of PF-06647020 as single 
agent treatment in patients with platinum-refractory or resistant OVCA and recurrent NSCLC 
(in approximately 20 patients) using mTPI method.  Successive cohorts of patients will 
receive doses of PF-06647020 starting at a dose of 2.1 mg/kg, Q2W. Once the RP2D is 
determined and preliminary efficacy is observed, dose expansions (Part 2) will be started to
further investigate safety, PK and efficacy of Q2W PF-06647020 in three cohorts of patients:

Cohort 1: PF-06647020 as a single agent treatment in patients with platinum resistant 
or refractory OVCA.

Cohort 2: PF-06647020 as a single agent treatment in patients with recurrent 
advanced NSCLC.

Cohort 3: PF-06647020 in combination with avelumab in platinum resistant or 
refractory OVCA.
Approximately 24 patients will be enrolled for each cohort.  Patients that were enrolled in the 
Part 1 single agent dose escalation will be counted as part of the 24 patients in their 
respective Part 2 single agent cohorts. An additional cohort in approximately 24 patients 
with recurrent advanced NSCLC receiving combination of PF-06647020 with avelumab may 
also be considered for inclusion at a later time, if supported by safety and anti-tumor activity 
observed in the single agent treatment cohort. 
In the combination expansion Cohort 3, the RP2D of PF-06647020 as determined by Part 1 
will be used as the dose to combine with avelumab at 800 mg (both administered IV, Q2W).  
The PF-06647020 dose may be reduced (but not further escalated) for safety reasons. After 
at least 6 patients in the combination cohort have completed a minimum observation period 
of 4 weeks, safety will be reviewed by the investigators and Pfizer (using the same DLT 
definition described in Section A4.2). If there are no safety concerns precluding continuation 
of the study, enrollment of the remaining patients for this cohort will proceed. If DLT is 
observed in 2 out of 6 patients, at least 6 additional patients will be enrolled at a reduced dose 
of PF-06647020 (the reduced dose of PF-06647020 could be one dose level below the 
defined RP2D from Part 1 assuming the RP2D is above the starting dose of Part 1 
(ie, 2.1 mg/kg), or 1.8 mg/kg of PF-06647020 in a circumstance that the RP2D from Part 1 is 
2.1 mg/kg).


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A total of approximately 72 patients will be enrolled in the Q2W regimen expansion. 
Patients will participate in the study for approximately 9 months or until disease progression, 
patient withdrawal of consent or unacceptable toxicity occurs, patient loss to follow up, or 
the study is terminated by the Sponsor, whichever comes first.  This includes a 4 week 
screening period, a 7 month treatment period and a 4 week post dose follow-up period.  A 
follow-up visit within 4 weeks after the last dose of study drug for adverse event AE and 
SAE collection will be conducted.  The time on study can vary depending on the observed 
toxicity and potential benefit an individual patient derives.  The study is expected to be 
completed in approximately 36 months. 
All study requirements and guidelines described in the main body of the protocol must be 
followed, in addition to any described in this Appendix 8.
A4.1. Dose Escalation 
The Q2W regimen expansion contains a PF-06647020 dose escalation portion (Part 1) using 
the mTPI method and details are included in Section 3.2 and Table 8.
Patients may be enrolled in cohorts of 2-4, starting with 2.1 mg/kg Q2W for the first cohort.  
In cohorts with 2 patients enrolled, an additional patient may be enrolled for dose escalation 
assessment if one of the two patients has a DLT.  If a high DLT rate (>33%) is observed at 
the starting dose, a lower dose may be considered.  The study may be stopped if the drug is 
deemed not tolerable at the lowest dose. Table 18 illustrates the potential dose levels in 
Part 1 dose escalation.
Table 18.
Table of Potential Dose Levels*
Dose Level
Dose
(mg/kg)
-1
TBD
1 (starting dose)
2.1
2
2.8
3
3.2
*additional intermediate doses may be investigated.
A4.2. DLT Definition for the Q2W Regimen
Severity of adverse events will be graded according to CTCAE version 4.03.  For the purpose 
of DLT assessment, any of the following adverse events occurring in the first cycle of 
treatment (within 28 days of first dose or until patient receives 2nd infusion if there are 
treatment delays) in the single agent dose escalation (Part 1) and combination of 
PF-06647020 with avelumab will be classified as DLTs, unless there is a clear alternative 
explanation (eg, related to underlying disease/progression).  DLTs in combination cohort(s) 
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(PF-06647020 with avelumab) will continue to be monitored for approximately 84 days for 
any late immune-related toxicities.

Hematologic:

Grade 4 neutropenia lasting >7 days;

Febrile neutropenia (ANC<1000/mm3 with a single temperature of >38.3 degrees 
C or a sustained temperature of 38 degrees C (100.4 degrees F) for more than 
one hour;

Grade 3 neutropenic infection; 

Grade 4 anemia;

Grade 3 thrombocytopenia with clinically significant bleeding
(ie, gastrointestinal bleeding requiring clinical intervention and all intracranial 
bleeding);

Grade 4 thrombocytopenia: 

any <10,000;

10,000-25,000 for > 3 days;

Treatment delay >14 days because of hematologic adverse event.

Hepatic:

Grade 3 serum bilirubin, hepatic transaminase (ALT or AST) or alkaline 
phosphatase.  For patients with Grade 2 hepatic transaminase or alkaline 
phosphatase levels at baseline as a result of liver metastasis or bone metastasis, a 
hepatic transaminase or alkaline phosphatase level > 10 x ULN will be considered 
as a DLT. 

ALT or AST 3.0 x ULN concurrent with elevation in bilirubin 2.0 x ULN.

Non-hematologic, non-hepatic:

Grade 3 toxicities that are considered non-hematologic, non-hepatic major organ 
toxicity (excluding alopecia of any grade, Grade 3 diarrhea and Grade 3 nausea 
and vomiting that responds to therapy). 

Delay by more than 2 weeks in receiving the next scheduled cycle due to 
persisting toxicities attributable to PF-06647020.

Grade 3 headache lasting >48 hours in presence of supportive care.


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In addition, clinically important or persistent toxicities lasting >5 days in presence of 
supportive care (eg, Grade 3 diarrhea) that are not included in the above criteria should be 
considered a DLT following review by Pfizer and the investigators.  All DLTs need to 
represent a clinically significant shift from baseline.
During Cycle 1 and subsequent cycles, primary use of granulocyte-colony stimulating factors 
is permitted following ASCO guidance, if ANC 1000/mm3. 
Primary prophylaxis of diarrhea, nausea and vomiting is permitted in the first cycle and 
subsequent cycles at the investigator’s discretion.
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 Pfizer. 
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.  
However, in circumstances of an event not related to study drug (eg, traffic accident, clear 
disease progression) that leads to study termination close to/before 28 days, the patient might 
be deemed evaluable if the investigators and Pfizer agree.
In the combination cohort (Part 2), the RP2D of PF-06647020 defined from Part 1 will be 
used to combine with avelumab 10 mg/kg, Q2W.  There will be no dose escalation for the 
combination cohorts.  Part 1 and Part 2 patients will be pooled for the evaluation of safety, 
tolerability and anti-tumor activity of PF-06647020.  In Part 2, OVCA patients will be 
randomized to receive the combination treatment (Cohort 3) or PF-06647020 single agent 
treatment cohort (Cohort 1) once Cohort 3 is open for enrollment. 
A4.2.1. Late Immune-Related DLTs
In the combination of PF-06647020 with avelumab Cohort 3, late immune-related DLTs are 
immune-related AEs that meet the same grading criteria as DLT criteria and occur from 
Day 29 through the Day 84 assessment period (or completion of first 3 cycles if a patient 
remains on treatment).  If late immune related DLTs occur, enrollment in dose expansion (if 
it has been started at the time the late immune related DLT is observed) will be placed on 
temporary hold.  All safety data will be reviewed by Pfizer and investigators, and a decision 
will be made to either:

Continue enrollment of dose expansion.

All 9 patients used for DLT assessment will be followed for at least 84 days to 
reassess safety.  The totality of patients with above described DLT and late immune 
related DLT will be used to reassess DLT rate and inform decision whether a lower 
dose of PF-06647020 should be considered to be combined with avelumab 
(10 mg/kg) to further investigate safety and tolerability.


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
Stop the combination study. 
A5. Assessments
Assessments that are captured in the Schedule of Activities but not described below may be 
found in the main body of the protocol and must be followed.
A5.1. Tumor Assessment
Anti-tumor activity will be assessed by radiological tumor assessments at 8-week intervals 
until documented disease progression, using RECIST version 1.1 for the single agent arms, 
and immune-related response criteria (irRECIST) Appendix 9 for combinations arm(s).  If 
PR or CR is observed and the response duration exceeded 6 months, tumor assessment can be 
assessed at a 12-week interval. 
For all patients radiologic tumor assessments must include chest, abdomen, and pelvis.
Single agent Cohorts 1 and 2: All radiographic images will be collected for potential 
retrospective central review. Additional information on diagnostic imaging procedures and 
collection will be included in the Imaging Manual.
Complete responses, partial responses and progressive disease must be confirmed on 
repeated imaging at least 4 weeks after initial documentation.  In addition, radiological tumor 
assessments will also be conducted whenever disease progression is suspected 
(eg, symptomatic deterioration), and at the time of End of Treatment/Withdrawal (if not done 
in the previous 4 weeks).  Brain CT or MRI scans are required at baseline only when there is 
a suspected brain metastasis.  A bone scan (bone scintigraphy) or fluorine-18
fluorodeoxyglucose positron emission tomography (18FDG-PET)/CT is required at baseline 
only if bone metastases are suspected, then every 16 weeks only if bone metastases are 
present at baseline.  Otherwise, bone imaging is required only if new bone metastases are 
suspected.  Bone imaging is also required at the time of CR confirmation for patients who 
have bone metastases. MRI is acceptable for bone imaging if consistent with local practice.
CA-125 will be assessed in a local lab every 4 weeks. CA-125 measurement alone will not 
be used as criteria for disease progression or response determination. 
In the Part 2 PF-06647020 combination with avelumab cohort (Cohort 3), any patient 
observed with disease progression (based on irRECIST) will require an additional tumor
assessment in >4 weeks in order to confirm disease progression.  Patients can stay in the 
study at the discretion of investigator and sponsor until progressive disease is confirmed by 
the investigator.  Details of tumor assessment for the combination cohort can be found in the 
section of Treatment after Initial Evidence of Radiologic Disease Progression (Part 2 
combination cohort).  


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A5.4. Pharmacokinetics/Immunogenicity Assessments 
A5.4.1. PK Assessments
Blood samples (4 mL whole blood) to provide approximately 2 mL of serum for 
measurement of serum PF-06380101 concentrations and blood samples (6 mL whole blood) 
to provide approximately 3 mL of serum for determination of ADC (PF-06647020) and total 
antibody (hu6M024 mAb) concentrations will be collected from all patients, in appropriately 
labeled tubes at times specified in the Schedule Of Activities.  
For determination of serum avelumab concentrations, blood samples (4 mL) to provide 
approximately 2 mL of serum will be collected from patients in combination cohort in 
appropriately labeled tubes at times specified in the Schedule Of Activities.
All efforts will be made to obtain the PK samples at the scheduled nominal time relative to 
dosing and according to windows provided in the Schedule Of Activities.  Samples obtained 
within 10% of the nominal time (eg, within 6 minutes of a 60 minute sample) will be 
considered protocol compliant, and the exact time of the sample collection will always be 
noted on the CRF.  If a scheduled blood sample collection cannot be completed for any 
reason, the missed sample time may be re scheduled with agreement of clinical investigators, 
patient and sponsor.  PK samples will be assayed using validated analytical methods in 
compliance with Pfizer standard operating procedures.  Details regarding the collection, 
processing, storage, and shipping of the blood samples will be provided in the Laboratory
Manual.
In addition to samples collected at the scheduled times, an additional blood sample should be 
collected from patients experiencing unexpected and/or serious AEs and the date and time 
should be documented in the CRF.
A5.4.2. Immunogenicity Assessment
Blood samples (6 mL) to provide approximately 3 mL of serum to detect ADA and Nab 
against PF-06647020 will be collected from all patients, into appropriately labeled tubes at 
times specified in the Schedule Of Activities.  
Blood samples (3.5 mL) to provide approximately 1.5 mL of serum to detect ADA and Nab 
against avelumab will be collected from patients in combination cohort, 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. Samples will be analyzed using validated analytical 
methods in compliance with Pfizer standard operating procedures. The ADA sample 
analysis will follow a tiered approach of screening, confirmation, and titer determination.  
Samples tested positive for ADA may also be characterized for Nab.


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A5.5. Translational and 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
ADC with avelumab may improve clinical outcomes. Dendritic cells, known 
to express PTK7, maybe activated by the auristatin payload resulting in activation and 
maturation of antigen specific T-cells. Dendritic cell activation will be assessed in a 
peripheral blood flow cytometry assay.  Additionally, internalization of PF-06647020 and 
delivery of the payload may result in immunogenic cell death (ICD). The potential 
PF-06647020 induced ICD may result in stimulation of anti-tumor immunity and improved 
responses to avelumab.  CD8+ lymphocyte infiltration in pre- and on-treatment biopsies will 
be utilized as a surrogate marker of ICD. As expression signature of ICD may also be 
investigated in pre- and on-treatment biopsies and peripheral blood. 
A5.5.1. Archived Tumor Biospecimens and De Novo Tumor Biopsies
Archived tumor tissue samples and de novo biopsies of primary and/or metastatic lesions 
(see Section 7.3.1) will be used to analyze candidate DNA, RNA, or protein markers, or 
relevant signature of markers for their ability to identify those patients who are most likely to 
benefit from treatment with the study drugs. 
Markers that may be analyzed include, but may not necessarily be limited to, the 
presence/absence of tumor-infiltrating CD8+ T lymphocytes and/or expression of PTK7 and 
PD-L1 within the tumor microenvironment by immunohistochemistry or other methodology. 
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 Additional 
information on tissue collection procedures can be found in the Study Manual.
 
 
 
 
 
 
 
 
  Details regarding the collection, processing, storage, and 
shipping of the blood samples will be provided in the Laboratory Manual.
A5.6. Electrocardiogram Measurements
A standard 12-lead (with a 10-second rhythm strip) tracing will be used for all ECGs. 
All patients participating in the combination regimen (Cohort 3) require a triplicate ECG 
measurement at screening.  On-treatment ECGs will be performed on Day 1 of Cycles 1, 2, 
and 3 pre-infusion and Day 15 of Cycle 1.  At each time point, three (3) consecutive 12-lead 
ECGs (triplicates) will be performed approximately 2 minutes apart to determine mean QTc 
(average of triplicates).  When coinciding with blood sample draws for PK, ECG assessment 
should be performed prior to blood sample collection, such that the blood sample is collected 
at the nominal time.  If a patient experiences a cardiac or neurologic AE (specifically 
syncope, dizziness, seizures, or stroke) triplicate ECGs should be obtained at time of the 
event.  If the mean QTcF is prolonged (>500 msec), the ECGs should be re-evaluated by a 
qualified person at the institution for confirmation and repeated as clinically indicated.  
Additional triplicate ECGs may be performed as clinically indicated.  Clinically significant 
findings seen on follow-up ECGs should be recorded as AEs. 
To ensure safety, if there is a finding of QTc >500 msec (ie, CTCAE Grade >2), then ECG 
must be reviewed by qualified personnel at the site as soon as the finding is made, including 
verifying that the machine reading is accurate and that the Fridericia correction formula is 
applied.  If manual reading verifies a rate corrected QTc of >500 msec, repeat ECG should be 
immediately performed at least two times approximately 2 to 4 minutes apart. 
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An electronic reading of prolonged QTc must be confirmed by manual reading.  Prior to 
conclusion that an episode of prolongation of the QTc interval is due to study treatment, 
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 QTc interval reverts to less than 500 msec, and in the 
judgment of investigator and sponsor is determined to be due to a cause other than study 
treatment, treatment may be continued with regular ECG monitoring.
A6. PATIENT ELIGIBILITY CRITERIA
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 nonmedical conditions should be taken into 
consideration when deciding whether a particular patient is suitable for this protocol.  
Patient eligibility should be reviewed and documented by an appropriate member of the 
investigator’s study team before patients are included in the study.  
A6.1. Inclusion Criteria
Patients (in both Part 1 and Part 2) must meet all of the following inclusion criteria to be 
eligible for enrollment into the study:
1. Histological diagnosis of the following:
a.
 
  Patients with 
adenocarcinoma subtype NSCLC should be tested for ALK alterations and EGFR 
mutations and have exhausted all FDA-approved available targeted therapies. 
b. Platinum-resistant or refractory advanced epithelial ovarian, fallopian tube, or 
peritoneal cancer.
i.
Patients must have received ≤2 prior lines of systemic anticancer therapy.¥
ii. Histologically confirmed and documented disease. The following histological 
types are eligible:
•
adenocarcinoma not otherwise specified (NOS);
•
clear cell adenocarcinoma;
•
endometriod adenocarcinoma;
•
malignant Brenner's tumour;
•
mixed epithelial carcinoma;
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•
mucinous adenocarcinoma;
•
serous adenocarcinoma;
•
transitional cell carcinoma;
•
undifferentiated carcinoma.
Platinum-resistant/refractory disease is defined as disease progression within 
180 days from the completion of a minimum of 4 platinum based therapy 
cycles (resistant), or lack of response or disease progression while receiving 
the most recent platinum-based therapy (refractory), respectively.
¥ One line of therapy is counted as an entire regimen taken until PD was observed. 
*
 
2. Measurable disease by investigator assessment with at least 1 unidimensional 
measurable lesion by RECIST v.1.1 that has not previously been irradiated.
3. At least 18 years of age.
4. ECOG performance status 0 to 2.
5. Estimated life expectancy of at least 3 months.
6.
 
 
 
 
 
7. Adequate bone marrow function, including:
a.
Absolute neutrophil count (ANC) ≥1.5 x 109/L;
b. Platelet count ≥100 x 109/L;
c.
Hemoglobin ≥9 g/dL (may have been blood transfused). 
8. Adequate liver function, including:
•
Total bilirubin level ≤1.5 × ULN;
•
AST and ALT ≤2.5 x ULN. 
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9. Adequate renal function as evidenced by: 
a.
Creatinine clearance 50 mL/min as calculated using the Cockcroft-Gault 
equation.
10. Serum/urine pregnancy test (for females of childbearing potential) negative at 
screening.
11. Female patients, of childbearing potential and at risk for pregnancy must agree to use 
two highly effective methods of contraception throughout the study and after the last 
dose of assigned treatment for the following lengths of time. 
a.
Patients who receive PF-06647020 alone: for at least 30 days after the last 
PF-06647020 dose.
b. Patients who receive PF-06647020 in combination with avelumab: for at least 
60 days after the last PF-06647020/avelumab dose.
12. Evidence of a personally signed and dated informed consent document indicating that 
the patient has been informed of all pertinent aspects of the study. 
13. Willing and able to comply with scheduled visits, treatment plan, laboratory tests and 
other study procedures.
A6.2. Exclusion Criteria
Patients (in both Part 1 and Part 2) with any of the following characteristics/conditions will 
not be included in the study:
1. OVCA patients: Non-epithelial tumor including malignant mixed Mullerian tumors or 
ovarian tumors with low malignant potential (ie, borderline tumors).
2. Prior therapy with an anti-PTK7 for the single agent treatment cohorts, and 
anti-PTK7, anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-cytotoxic 
T lymphocyte-associated antigen 4 (CTLA 4) antibody (including ipilimumab, 
tremelimumab or any other antibody or drug specifically targeting T-cell 
co-stimulation or immune checkpoint pathways) for combination Cohort 3 in OVCA.
3. Known symptomatic brain metastases requiring steroids.  Patients with previously 
diagnosed brain metastases are eligible if they have completed their treatment and 
have recovered from the acute effects of radiation therapy or surgery prior to study 
entry, have discontinued corticosteroid treatment for these metastases for at least 
4 weeks prior to study entry and are neurologically stable. 


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4. Concurrent anticancer treatment within 28 days prior to study entry, eg, cytoreductive 
therapy, radiotherapy [with the exception of palliative radiotherapy], immunotherapy, 
or cytokine therapy (except for erythropoietin); major surgery within 28 days prior to 
study entry (excluding diagnostic biopsy); use of hormonal agents within 7 days prior 
to study entry; or use of any investigational drug within 28 days prior to study entry.  
Note: patients receiving bisphosphonate or denosumab are eligible provided treatment 
was initiated at least 14 days prior to study entry.
5. Diagnosis of any other malignancy within 5 years prior to registration, except for 
adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the 
breast or of the cervix.
6. Any one of the following currently or in the previous 6 months: myocardial 
infarction, congenital long QT syndrome, Torsades de Pointes, arrhythmias (including 
sustained ventricular tachyarrhythmia and ventricular fibrillation, bradycardia defined 
as <50 bpm), right bundle branch block and left anterior hemiblock (bifascicular 
block), unstable angina, coronary/peripheral artery bypass graft, symptomatic 
congestive heart failure (New York Heart Association Class III or IV), 
cerebrovascular accident, transient ischemic attack or symptomatic pulmonary 
embolism. 
7. Ongoing cardiac dysrhythmias of NCI CTCAE Grade 3, atrial fibrillation of any 
grade, or QTcF interval >470 msec at screening (average of triplicate ECG). 
8. Prior organ transplantation including allogeneic stem-cell transplantation.
9. Prior treatment with a compound of the same mechanism.
10. Currently receiving active treatment in another clinical study.
11. Known history of a positive test for HIV or AIDS related illness. 
12. Active infection requiring systemic therapy.
13. HBV or HCV infection at screening (positive HBV surface antigen or HCV RNA if 
anti-HCV antibody screening test positive). 
14. Administration of a live vaccine within 30 days prior to study entry.
15. Current or prior use of immunosuppressive medication within 7 days prior to 
randomization.  The following are exceptions to this exclusion criterion:
a.
Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra-articular 
injection).
16. Systemic corticosteroids at physiologic doses exceed 10 mg/day of prednisone or 
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17. Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication). 
18. Active autoimmune disease that might deteriorate when receiving an 
immunostimulatory agents.  Patients with diabetes type I, vitiligo, psoriasis, hypo- or 
hyperthyroid disease not requiring immunosuppressive treatment are eligible.
19. Known severe hypersensitivity reactions to monoclonal antibodies or liposomal 
preparations.  Known hypersensitivity to any component of the Investigational 
Products.
20. Persisting Grade 2 toxicity related to prior therapy; however, Grade 2 sensory 
neuropathy or alopecia is acceptable. 
21. Severe gastrointestinal conditions such as clinical or radiological evidence of bowel 
obstruction within 4 weeks prior to study entry, uncontrolled diarrhea in the last 
4 weeks prior to enrollment, or history of inflammatory bowel disease.
22. Known current alcohol or drug abuse at the time of screening.
23. 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.
24. Current use or anticipated need for treatment with drugs or foods that are known 
strong CYP3A4 inhibitors, (eg, grapefruit juice or grapefruit/grapefruit-related citrus 
fruits (eg, Seville oranges, pomelos), ketoconazole, miconazole, itraconazole, 
voriconazole, posaconazole, clarithromycin, telithromycin, indinavir, saquinavir, 
ritonavir, nelfinavir, amprenavir, fosamprenavir nefazodone, lopinavir, 
troleandomycin, mibefradil, and conivaptan) or inducers (eg, rifampin, St. John’s 
Wort, phenobarbital, and phenytoin) including their administration within 10 days 
prior to patient registration. The topical use of these medications (if applicable), such 
as 2% ketoconazole cream, is allowed (see Appendix 6).
25. Other acute or chronic medical or psychiatric condition including recent (within the 
past year) or active suicidal ideation or behavior or laboratory abnormality that may 
increase the risk associated with study participation or investigational product 
administration or may interfere with the interpretation of study results and, in the 
judgment of the investigator, would make the patient inappropriate for entry into this 
study.
26. UK Only: Male patients with female partners of childbearing potential who are 
unwilling to use a highly effective method of contraception as described in this 
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27. UK Only: Male patients who are unwilling or unable to use 2 highly effective
methods of contraception as described in this protocol for the duration of the study 
and for 120 days after the last dose of investigational product (150 days if the male 
patient is participating in the combination cohort with avelumab). 
28. Pregnant female patients; breastfeeding female patients; 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 
30 days after the last dose of investigational product (60 days if the female patient is 
participating in the combination cohort with avelumab). 
Female patients of nonchildbearing potential must meet at least 1 of the following criteria:

Achieved postmenopausal status, defined as follows: cessation of regular menses for 
at least 12 consecutive months with no alternative pathological or physiological 
cause; status may be confirmed with a serum FSH level confirming the 
postmenopausal state;

Have undergone a documented hysterectomy and/or bilateral oophorectomy; 

Have medically confirmed ovarian failure. 
All other female patients (including female patients with tubal ligations) are considered to 
be of childbearing potential.
A7. STUDY TREATMENTS
A7.1. Avelumab
Avelumab is a sterile, clear, and colorless solution intended for IV administration.  Avelumab 
is formulated as a 20 mg/mL solution and is supplied by the Sponsor in single-use glass vials, 
stoppered with a rubber septum and sealed with an aluminum polypropylene flip-off seal.
Avelumab (MSB0010718C) will be supplied for the study by Pfizer Global Clinical Supply, 
Worldwide Research and Development.
Packaging and labeling will be in accordance with applicable local regulatory requirements 
and applicable Good Manufacturing Practice (GMP) guidelines.  Avelumab will be packed in 
boxes each containing one vial.  The information on the study treatment will be in 
accordance with approved submission documents. 
Avelumab will be shipped in transport cool containers (2C to 8C) that are monitored with 
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A7.2. Preparation, Dispensing and Administration
See the Investigational Product Manual (IP Manual) for instructions on how to prepare the 
investigational product for administration.  Investigational product should be prepared and 
dispensed by an appropriately qualified and experienced member of the study staff 
(eg, physician, nurse, physician’s assistant, nurse practitioner, pharmacy assistant/technician, 
or pharmacist) as allowed by local, state, and institutional guidance.  
Only qualified personnel who are familiar with procedures that minimize undue exposure to 
themselves and to the environment should undertake the preparation, handling, and safe 
disposal of the investigational agents.  
A7.2.1. PF-06647020 Administration
PF-06647020 will be administered on Day 1 and 15 of each 4-week cycle as an IV infusion 
over approximately 60 minutes on an outpatient basis. A cycle is defined as the time from 
Day 1 dose to the next Day 1 dose.  
Details for preparation and administration of the PF-06647020 infusion are provided in the IP
Manual.  All patients should be weighed within 72 hours prior to dosing for every cycle to 
ensure they did not experience either a weight loss or gain >10% from the prior weight used 
to calculate the amount of PF-06647020 required for dose preparation.  The decision to 
recalculate PF-06647020 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 initial dose, the amount of 
PF-06647020 required for preparation and administration for the current cycle must be 
recalculated using this most recent weight obtained.
Sites should make every effort to target PF-06647020 infusion timing to be as close to 1 hour 
as possible.  However, given the variability of infusion pumps from site to site, time windows 
of -10/+20 minutes is permitted (ie, infusion time is 50-80 minutes).  The exact duration of 
infusion should be recorded in both source documents and CRFs. 
A7.2.2. Avelumab Administration
Avelumab will be administered as a 1-hour IV infusion once every 14 days.  Details for 
preparation and administration of the avelumab infusion are provided in the IP Manual.  
Avelumab will be administered at 800 mg on Day 1 and Day 15 of each 4-week cycle after 
all procedures/assessments have been completed as described in the SOA table.  Avelumab 
may be administered up to 3 days before or after the scheduled day of administration of each 
cycle due to administrative reasons.
For the combination arm, where both PF-06647020 and avelumab are infused (Q2W) 
avelumab will be infused after PF-06647020.  If premedication was administered prior to 
PF-06647020, the decision whether to repeat pre-medication prior to avelumab is at the 
discretion of the investigator depending on the elapsed time and the half-life of 


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corresponding premedication agent.  The line should be flushed, according to local practice, 
between infusions, and a new administration set should be used for avelumab. 
Sites should make every effort to target avelumab infusion timing to be as close to 1 hour as 
possible.  However, given the variability of infusion pumps from site to site, time windows of 
minus 10 minutes and plus 20 minutes is permitted (ie, infusion time is 50-80 minutes).  The 
exact duration of infusion should be recorded in both source documents and CRFs.  Possible 
modifications of the infusion rate for the management of infusion-related reactions are 
described in the Guidelines for Toxicity Management (below).
A7.2.2.1. Mandatory Premedication for Avelumab Administration
In order to mitigate infusion-related reactions, a premedication with an antihistamine and 
with paracetamol (acetaminophen) 30 to 60 minutes prior to each dose of avelumab is 
mandatory (for example, 25-50 mg diphenhydramine and 500-650 mg paracetamol IV or 
oral).  This may be modified based on local treatment standards and guidelines, as 
appropriate. The pre-treatment medications will not be supplied by Pfizer.
A7.2.2.2. Treatment after Initial Evidence of Radiologic Disease Progression (Part 2 
Combination Cohort 3)
In the combination of PF-06647020 and avelumab Cohort 3 in Part 2, immunotherapeutic 
agents such as avelumab may produce anti-tumor effects by potentiating endogenous 
cancer-specific immune responses.  The response patterns seen with such an approach may 
extend beyond the typical time course of responses seen with PF-06647020, and may 
manifest as a clinical response after an initial increase in tumor burden or even the 
appearance of new lesions. 
All patients receiving the combination that demonstrate progression at initial scan (based on 
RECIST 1.1 and/or irRECIST), an additional tumor assessment should be repeated 4 weeks 
later and assessed in order to confirm progression.  Single agent avelumab may be continued 
at the Investigator’s discretion while awaiting radiologic confirmation (ie, expedited central 
review) of disease progression.  If repeat imaging no longer shows PD but rather CR, PR, or 
SD compared to the baseline scan, treatment may be continued/resumed.  In determining 
whether or not the tumor burden has increased or decreased, Investigators should consider all 
target lesions as well as non-target lesions (refer to the Study Manual). 
Before continuation of treatment, the patient must provide consent and be informed that in 
order to continue receiving the investigational products on study, the patient may be 
foregoing approved therapy with possible clinical benefit(s).  Patients may receive avelumab 
while waiting for confirmation of PD if they are clinically stable as defined by the following 
criteria: 

Absence of clinical signs and symptoms (including worsening of laboratory values) 
of disease progression. 

No decline in ECOG performance status. 


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
Absence of rapid progression of disease by radiographic imaging. 

Absence of progressive tumor at critical anatomical sites (eg, cord compression) 
requiring urgent alternative medical intervention.
If repeat imaging demonstrates confirmed evidence of PD, patients should be discontinued 
from all study treatment.  However, according to the Investigator’s clinical judgment and 
after discussion between the Investigator and the Sponsor, if a patient with evidence of PD is 
still experiencing clinical benefit, the patient may be eligible for continued treatment with 
single agent avelumab if above criteria are met.   The Investigator’s judgment should be 
based on the overall benefit-risk assessment and the patient’s clinical condition, including 
performance status, clinical symptoms, AEs, and laboratory data.  
A7.2.3. Food Requirements
All study drugs may be administered without regard to food.
A7.3. Guidelines for Toxicity Management 
A7.3.1. PF-06647020: Dose Interruptions/Delays 
Patients experiencing Grade 3 or 4 potentially treatment related toxicity or intolerable 
Grade 2 toxicity despite supportive care should have their treatment interrupted/delayed.  
Appropriate follow up assessments should be done until adequate recovery occurs as 
assessed by the investigator. 
If a treatment interruption continues beyond Day 28 of the current cycle, then the day when 
treatment is restarted will be counted as Day 1 of the next cycle.  Re-treatment following 
treatment interruption for treatment related toxicity or at the start of any new cycle may not 
occur until all of the following parameters have been met:

ANC 1,000/mm3. 

Platelets count 75,000/mm3. 

Non-hematologic toxicities have returned to baseline or Grade 1 severity (or, at the 
investigator discretion, Grade 2 if not considered a safety risk for the patient).
If these conditions are not met, treatment must be delayed by 1 week.  If, after a 1-week 
delay, all toxicities have recovered within the limits described above treatment with 
PF-06647020 can be resumed.  
Initiation of the next cycle can only be delayed by a maximum of 2 weeks.  Therefore, if 
persisting toxicity does not allow PF-06647020 treatment resumption within 28 days of 
previous dose administration, this will result in discontinuation of the patient from treatment 
unless discussed and agreed with the Sponsor.


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A7.3.1.1. PF-06647020: Dose Reductions  
Following dose interruption or cycle delay due to toxicity, PF-06647020 may need to be 
reduced when treatment is resumed. Patients may have PF-06647020 reduced to 1.8 mg/kg, 
but no further reductions are allowed.  Once a dose has been reduced for a given patient, all 
subsequent cycles should be administered at that dose level. Dose re-escalation is not 
allowed. 
Refer to Section 5.4.3 for additional guidance on dose reductions.
A7.3.2. PF-06647020 in Combination with Avelumab
For patients receiving PF-06647020 and avelumab combination, PF-06647020 dose 
modifications as well as infusion omissions/delays for PF-06647020 and/or avelumab may 
occur independently for the two drugs according to the guidance provided (see Table 10 and 
Table 22) and according to investigator’s medical judgment. Modifications will be reported 
in the CRF. Patients may have PF-06647020 reduced to 1.8 mg/kg (assuming 2.1 mg/kg is 
the RP2D for the Q2W dosing schedule) or one dose level below the RP2D determined in the 
single agent treatment lead-in study (Part 1), no further reductions are allowed.  Once a dose 
has been reduced for a given patient, all subsequent cycles should be administered at that 
dose level. 
Dose re-escalation is not allowed. 
If PF-06647020 is delayed by 1 week, avelumab should also be delayed by 1 week so that 
PF-06647020 and avelumab are administered together.  
For patients experiencing an AE related to PF-06647020 that fails to recover to CTCAE 
Grade 1 (or within 1 grade of starting values for pre-existing laboratory abnormalities) 
leading to treatment delay of >2 weeks should be discontinued unless discussed with the 
Sponsor. Recommended dose modifications are illustrated in Table 10.
For avelumab, no dose modifications are permitted in this study, but doses may be omitted 
based on persisting toxicity. 
A7.3.3. Guidelines for Avelumab Toxicity Management 
A7.3.3.1. Avelumab: Adverse Drug Reactions Requiring Discontinuation or Delays
The following adverse drug reactions (ADRs), if considered to be related with avelumab 
treatment, require permanent treatment discontinuation of avelumab:
Any Grade 4 ADRs require permanent treatment discontinuation with avelumab except for 
single laboratory values out of normal range that are unlikely related to trial treatment as 
assessed by the Investigator, do not have any clinical correlate, and resolve within 7 days 
with adequate medical management.


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Any Grade 3 ADRs require permanent treatment discontinuation of avelumab except for any 
of the following: 

Transient (6 hours) Grade 3 flu-like symptoms or fever, which are controlled with 
medical management.

Transient (24 hours) Grade 3 fatigue, local reactions, headache, nausea, or emesis 
that resolve to Grade 1. 

Transient Grade 3 diarrhea (24 hours) that resolves to Grade 1 or less without 
administration of steroids.

Single laboratory values out of normal range (excluding Grade 3 liver function test 
increase) that are unlikely related to trial treatment according to the Investigator, do 
not have any clinical correlate, and resolve to Grade 1 within 7 days with adequate 
medical management.

Tumor flare phenomena defined as local pain, irritation, or rash localized at sites of 
known or suspected tumor.

Change in ECOG PS to 3 that resolves to 2 within 14 days (infusions should not be 
given on the following cycle, if the ECOG PS is 3 on the day of trial drug 
administration).
For any Grade 2 ADR, avelumab dosing should be managed as follows:

If a Grade 2 ADR resolves to Grade 1 prior to the next scheduled dose, treatment 
may continue.

If a Grade 2 ADR does not resolve to Grade 1 prior to the next scheduled dose, 
infusions should be withheld.  If by the following scheduled infusion the event has 
not resolved to Grade 1, the patient should permanently discontinue treatment (except 
for hematological toxicities and hormone insufficiencies, that can be managed by 
replacement therapy; for these hormone insufficiencies, up to 2 subsequent doses may 
be omitted).

Upon the second occurrence of the same Grade 2 ADR (except for hormone 
insufficiencies that can be managed by replacement therapy or hematologic toxicities) 
in the same patient, treatment with avelumab has to be permanently discontinued.
Avelumab infusion-related reactions, hypersensitivity reactions (Grades 1 to 4), tumor lysis 
syndrome, and irAEs should be handled according to guidelines provided below.


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A7.3.3.2. Avelumab: Infusion-related Reactions and Hypersensitivity Reactions
As with all monoclonal antibody therapies, there is a risk of allergic reactions including 
anaphylactic shock.  Avelumab should be administered in a setting that allows for immediate 
access to an intensive care unit or equivalent environment and administration of therapy for 
anaphylaxis, such as the ability to implement immediate resuscitation measures.  Steroids 
(dexamethasone 10 mg), epinephrine (1:1,000 dilution), allergy medications 
(IV antihistamines), bronchodilators, or equivalents, and oxygen should be available for 
immediate access.
Infusion of avelumab will be stopped in case of Grade 2 infusion-related, allergic, or 
anaphylactic reactions.  Following the first 4 avelumab infusions, patients must be observed 
for 2 hours post-infusion for potential infusion-related reactions.  If no infusion reaction 
occurs in relation to the first 4 infusions, the post-infusion observation period may be 
discontinued.  During this 2-hour observation period the patient should remain in a location 
where they can be observed by site staff.  Vital sign measurements or other procedures are 
not required unless clinically indicated.  If an allergic reaction occurs, the patient must be 
treated according to the best available medical practice.  The emergency treatment of 
anaphylactic reactions according to the Working Group of the Resuscitation Council (United 
Kingdom) can be found at https://www.resus.org.uk/pages/reaction.pdf.  Patients should be 
instructed to report any delayed reactions to the Investigator immediately. 
Table 19.
Avelumab: Treatment Modifications for Symptoms of Infusion-related 
Reactions
NCI-CTCAE Grade 
Treatment Modification for Avelumab
Grade 1 – mild
Mild transient reaction; infusion interruption not indicated; 
intervention not indicated.
Decrease Avelumab infusion rate by 50% and monitor 
closely for any worsening.
Grade 2 – moderate
Therapy or infusion interruption indicated but responds 
promptly to symptomatic treatment (eg, antihistamines, 
NSAIDs, narcotics, IV fluids); prophylactic medications 
indicated for 24 hours.
Stop Avelumab infusion.
Resume infusion at 50% of previous rate once 
infusion-related reaction has resolved or decreased to at 
least Grade 1 in severity, and monitor closely for any 
worsening.
Grade 3 or Grade 4 – severe or life-threatening
Grade 3: Prolonged (eg, not rapidly responsive to 
symptomatic medication and/or brief interruption of 
infusion); recurrence of symptoms following initial 
improvement; hospitalization indicated for clinical 
sequelae.
Grade 4: Life-threatening consequences; urgent 
intervention indicated.
Stop the Avelumab infusion immediately and disconnect 
infusion tubing from the patient.
Patients have to be withdrawn immediately from 
Avelumab treatment and must not receive any further 
Avelumab treatment.
IV=intravenous, NCI-CTCAE=National Cancer Institute-Common Terminology Criteria for Adverse Event, 
NSAIDs=nonsteroidal anti-inflammatory drugs.


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Once the Avelumab infusion rate has been decreased by 50% due to an infusion-related 
reaction, it must remain decreased for all subsequent infusions.
A7.3.3.3. Avelumab: Additional Modifications for Patients with Grade 2 
Infusion-related Reactions
If, in the event of a Grade 2 infusion-related reaction that does not improve or worsens after 
implementation of the modifications indicated in Table 19 (including reducing the infusion 
rate by 50%), the investigator may consider treatment with corticosteroids and the infusion 
should be stopped for that day.  At the next cycle, the investigator may consider the addition 
of H2-blocker antihistamines (eg, famotidine or ranitidine), in addition to the mandatory 
premedication.  However, prophylactic steroids are NOT permitted.  If the patient has a 
second infusion-related reaction Grade 2 on the slower infusion rate, with or without the 
addition of further medication to the mandatory premedication, the infusion should be 
stopped and the patient removed from avelumab treatment.
A7.3.3.4. Avelumab: Severe Hypersensitivity Reactions and Flu-like Symptoms
If hypersensitivity reaction occurs, the patient must be treated according to the best available 
medical practice.  A complete guideline for the emergency treatment of anaphylactic 
reactions according to the Working Group of the Resuscitation Council (United Kingdom) 
can be found at https://www.resus.org.uk/pages/reaction.pdf.  Patients should be instructed to 
report any delayed reactions to the Investigator immediately.
Symptoms include impaired airway, decreased oxygen saturation (<92%), confusion, 
lethargy, hypotension, pale or clammy skin, and cyanosis.  These symptoms can be managed 
with epinephrine injection and dexamethasone.  Patients should be placed on monitor 
immediately, and the intensive care unit should be alerted for possible transfer if required.
For prophylaxis of flu-like symptoms, 25 mg of indomethacin or comparable nonsteroidal 
anti-inflammatory drug (NSAID) dose (eg, ibuprofen 600 mg, naproxen sodium 500 mg) 
may be administered 2 hours before and 8 hours after the start of each dose of avelumab IV 
infusion.  Alternative treatments for fever (eg, paracetamol) may be given to patients at the 
discretion of the investigator.
A7.3.3.5. Avelumab: Immune-related Adverse Events
Because inhibition of PD-L1 stimulates the immune system, irAEs may occur.  Treatment of 
irAEs is mainly dependent upon severity (NCI-CTCAE grade):

Grades 1 to 2: treat symptomatically or with moderate dose steroids, more frequent 
monitoring.

Grades 1 to 2 (persistent): manage similar to high grade AE (Grades 3 to 4).

Grades 3 to 4: treat with high dose corticosteroids.


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For patients receiving PF-06647020 and avelumab combination, any event suspected to be 
immune-related should be managed according to the guidance for management of 
immune-related AEs in Table 20.  
Table 20.
Avelumab: Management of Immune-related Adverse Events
Gastrointestinal irAEs
Severity of Diarrhea/Colitis
(NCI-CTCAE v4.03)
Management
Follow-up
Grade 1
Diarrhea: <4 stools/day over Baseline
Colitis: asymptomatic 
Continue avelumab therapy
Symptomatic treatment 
(eg, loperamide)
Close monitoring for worsening symptoms
Educate patient to report worsening 
immediately
If worsens:
Treat as Grade 2 or 3/4 
Grade 2
Diarrhea: 4 to 6 stools per day over 
Baseline; IV fluids indicated 
<24 hours; not interfering with ADL
Colitis: abdominal pain; blood in 
stool 
Delay avelumab therapy
Symptomatic treatment
If improves to Grade 1: 
Resume avelumab therapy
If persists >5 to 7 days or recur:
0.5 to 1.0 mg/kg/day methylprednisolone or 
equivalent 
When symptoms improve to Grade 1, taper 
steroids over at least 1 month, consider 
prophylactic antibiotics for opportunistic 
infections, and resume avelumab therapy per 
protocol.
If worsens or persists >3 to 5 days with oral 
steroids:
Treat as Grade 3 to 4
Grade 3 to 4
Diarrhea (Grade 3): 7 stools per day 
over Baseline; incontinence; IV fluids 
24 hrs; interfering with ADL
Colitis (Grade 3): severe abdominal
pain, medical intervention indicated, 
peritoneal signs
Grade 4: life-threatening, perforation
Discontinue avelumab therapy 
per protocol
1.0 to 2.0 mg/kg/day 
methylprednisolone IV or 
equivalent
Add prophylactic antibiotics for 
opportunistic infections 
Consider lower endoscopy 
If improves: 
Continue steroids until Grade 1, then taper 
over at least 1 month
If persists >3 to 5 days, or recurs after 
improvement:
Add infliximab 5 mg/kg (if no 
contraindication), Note: Infliximab should not 
be used in cases of perforation or sepsis 
Dermatological irAEs
Grade of Rash
(NCI-CTCAE v4.03)
Management
Follow-up
Grades 1 to 2 
Covering 30% body surface area 
Symptomatic therapy (for 
example, antihistamines, topical 
steroids) 
Continue avelumab therapy
If persists >1 to 2 weeks or recurs: 
Consider skin biopsy 
Delay avelumab therapy
Consider 0.5 to 1.0 mg/kg/day 
methylprednisolone IV or oral equivalent.  
Once improving, taper steroids over at least 
1 month, consider prophylactic antibiotics for 
opportunistic infections, and resume avelumab 
therapy
If worsens: 
Treat as Grades 3 to 4 


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Grades 3 to 4
Covering >30% body surface area; 
life threatening consequences
Delay or discontinue avelumab 
therapy
Consider skin biopsy 
Dermatology consult 
1.0 to 2.0 mg/kg/day 
methylprednisolone IV or IV 
equivalent 
If improves to Grade 1: 
Taper steroids over at least 1 month and add 
prophylactic antibiotics for opportunistic 
infections 
Resume avelumab therapy
Pulmonary irAEs
Grade of Pneumonitis
(NCI-CTCAE v4.03)
Management
Follow-up
Grade 1
Radiographic changes only 
Consider delay of avelumab 
therapy 
Monitor for symptoms every 
2 to 3 days 
Consider Pulmonary and 
Infectious Disease consults 
Re-image at least every 3 weeks
If worsens: 
Treat as Grade 2 or Grade 3 to 4 
Grade 2
Mild to moderate new symptoms 
Delay avelumab therapy
Pulmonary and Infectious 
Disease consults
Monitor symptoms daily, 
consider hospitalization 
1.0 mg/kg/day 
methyl-prednisolone IV or oral 
equivalent 
Consider bronchoscopy, lung 
biopsy 
Re-image every 1 to 3 days 
If improves: 
When symptoms return to near Baseline, taper 
steroids over at least 1 month and then resume 
avelumab therapy and consider prophylactic 
antibiotics
If not improving after 2 weeks or worsening: 
Treat as Grade 3 to 4 
Grade of Pneumonitis
(NCI-CTCAE v4.03)
Management
Follow-up
Grades 3 to 4
Severe new symptoms; New / 
worsening hypoxia; life-threatening 
Discontinue avelumab therapy
Hospitalize 
Pulmonary and Infectious 
Disease consults
2 to 4 mg/kg/day 
methylprednisolone IV or IV 
equivalent 
Add prophylactic antibiotics for 
opportunistic infections 
Consider bronchoscopy, lung 
biopsy 
If improves to Baseline: 
Taper steroids over at least 6 weeks 
If not improving after 48 hours or worsening: 
Add additional immunosuppression (for 
example, infliximab, cyclophosphamide, IV 
immunoglobulin, or mycophenolate mofetil). 
Hepatic irAEs
Grade of Liver Test Elevation
(NCI-CTCAE v4.03)
Management
Follow-up
Grade 1
Grade 1 AST or ALT > ULN to 
3.0 x ULN and / or total bilirubin 
> ULN to 1.5 x ULN 
Continue avelumab therapy
Continue liver function monitoring 
If worsens: 
Treat as Grades 2 or 3 to 4 
Grade 2
AST or ALT >3.0 to 5 x ULN and / 
or total bilirubin >1.5 to 3 x ULN 
Delay avelumab therapy
Increase frequency of 
monitoring to every 3 days 
If returns to Baseline: 
Resume routine monitoring, resume avelumab 
therapy
If elevations persist >5 to 7 days or worsen: 


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0.5 to 1 mg/kg/day methylprednisolone or oral 
equivalent and when LFT returns to Grade 1 or 
Baseline, taper steroids over at least 1 month, 
consider prophylactic antibiotics for 
opportunistic infections, and resume avelumab 
therapy
Grades 3 to 4
AST or ALT >5 x ULN and / or total 
bilirubin >3 x ULN 
Discontinue avelumab therapy 
Increase frequency of 
monitoring to every 1 to 2 days 
1.0 to 2.0 mg/kg/day 
methylprednisolone IV or IV 
equivalent
Add prophylactic antibiotics for 
opportunistic infections 
Consult gastroenterologist
Consider obtaining MRI/CT 
scan of liver and liver biopsy if 
clinically warranted
If returns to Grade 2: 
Taper steroids over at least 1 month 
If does not improve in >3 to 5 days, worsens or 
rebounds: 
Add mycophenolate mofetil 1 gram (g) twice 
daily 
If no response within an additional 3 to 5 days, 
consider other immunosuppressants per local 
guidelines. 
Cardiac irAEs
Myocarditis
Management
Follow-up
New onset of cardiac signs or 
symptoms and / or new laboratory 
cardiac biomarker elevations 
(eg, troponin, CK-MB, BNP) or 
cardiac imaging abnormalities 
suggestive of myocarditis.
Withhold avelumab therapy
Hospitalize in the presence of
life threatening cardiac
decompensation, consider
transfer to a facility
experienced in advanced
heart failure and arrhythmia
management
Cardiology consult to
establish etiology and rule out
immune-mediated
myocarditis.
Guideline based supportive
treatment as per cardiology
consult.*
Consider myocardial biopsy if
recommended per cardiology
consult.
If symptoms improve and immune-mediated 
etiology is ruled out, re-start avelumab therapy.
If symptoms do not improve/worsen, viral
myocarditis is excluded, and immune mediated 
etiology is suspected or confirmed following 
cardiology consult, manage as 
immune-mediated myocarditis.
Immune-mediated myocarditis
Permanently discontinue 
avelumab.
Guideline based supportive 
treatment as appropriate as per 
cardiology consult.*
Methylprednisolone 1 to 
2 mg/kg/day
Once improving, taper steroids over at least 
1 month and add prophylactic antibiotics for 
opportunistic infections.
If no improvement or worsening, consider 
additional immunosuppressants 
(eg, azathioprine, cyclosporine A)
*Local guidelines, or eg. ESC or AHA guidelines
ESC guidelines website: https://www.escardio.org/Guidelines/Clinical-Practice-Guidelines
AHA guidelines website:
http://professional.heart.org/professional/GuidelinesStatements/searchresults.jsp?q=&y=&t=1001


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Endocrine irAEs
Endocrine Disorder
Management
Follow-up
Asymptomatic TSH abnormality 
Continue avelumab therapy 
If TSH <0.5 x LLN, or TSH >2 x ULN, or consistently out of range in 
2 subsequent measurements: include T4 at subsequent cycles as clinically 
indicated; consider endocrinology consult 
Symptomatic endocrinopathy 
Evaluate endocrine function 
Consider pituitary scan 
Symptomatic with abnormal 
lab / pituitary scan: 
Delay avelumab therapy
1 to 2 mg/kg/day 
methylprednisolone IV or by 
mouth equivalent 
Initiate appropriate hormone 
therapy 
No abnormal lab/pituitary MRI 
scan but symptoms persist: 
Repeat labs in 1 to 3 
weeks/MRI in 1 month 
If improves (with or without hormone 
replacement): 
Taper steroids over at least 1 month and 
consider prophylactic antibiotics for 
opportunistic infections 
Resume avelumab therapy 
Patients with adrenal insufficiency may need to 
continue steroids with mineralocorticoid 
component. 
Suspicion of adrenal crisis (for 
example, severe dehydration, 
hypotension, shock out of proportion 
to current illness) 
Delay or discontinue avelumab therapy 
Rule out sepsis 
Stress dose of IV steroids with mineralocorticoid activity 
IV fluids 
Consult endocrinologist 
If adrenal crisis ruled out, then treat as above for symptomatic endocrinopathy 
ADL=activities of daily living, ALT=alanine aminotransferase, AST=aspartate aminotransferase, CT=computed 
tomography; irAE=immune-related adverse event, IV=intravenous, LFT=liver function test, LLN=lower limit 
of normal, MRI=magnetic resonance imaging, NCI-CTCAE=National Cancer Institute-Common Terminology 
Criteria for Adverse Event, anti-inflammatory drugs, T4=free thyroxine, TSH=thyroid-stimulating hormone, 
ULN=upper limit of normal.
A7.3.3.6. Guidelines PF-06647020-Avelumab Combination Toxicity Management 
Dose modification (dose delays and dose reduction) for PF-06647020 due to ADRs should be 
made in accordance with the guidance provided below.  The starting dose for PF-06647020 
in combination will be the RP2D dose as determined by the single agent Q2W dose 
escalation (Part 1).  Dose reduction levels are described in Table 21.  
Some potential irAEs described with anti-PD-L1 drugs such as avelumab may overlap with 
PF-06647020 toxicities such as fatigue, nausea, or rash. For patients on combination 
treatment with avelumab and PF-06647020, any AE suspected to be immune-related should 
be managed according to the guidance for management of irAEs (Table 19).  In case of a 
potential irAE, besides the management related to avelumab therapy, PF-06647020 may also 
be reduced or interrupted.


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Table 21.
PF-06647020 Dose Modifications 
Starting Dose Level of 
PF-06647020
Dose Reduction
If RP2D is 2.8 mg/kg
2.1 mg/kg
If RP2D is 2.1 mg/kg
1.8 mg/kg
A7.3.3.7. PF-06647020-Avelumab Combination: Neutropenia  
ANC must be 1.0 x 109/L prior to each administration.  For patients who do not achieve 
hematological recovery on the scheduled day of PF-06647020 administration, complete 
blood counts should be performed twice weekly until the above defined limits are achieved.  
If hematological recovery is achieved within 14 days after the scheduled day of PF-06647020 
administration, resume PF-06647020 at the previous dose.  If hematological recovery is not 
achieved 14 days or more after the scheduled day of PF-06647020 administration, the patient 
will discontinue treatment unless discussed and agreed with the Sponsor.  Administration of 
G-CSF or EPO is permitted according to approved indications and scientific
recommendations.


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Table 22.
PF-06647020-Avelumab Combination: Treatment Modification for 
Neutropenia 
Neutropenia and 
Thrombocytopenia
PF-06647020 
Single Agent
PF-06647020-Avelumab Combination*
Grade 1
No PF-06647020 
dose reduction/delay
No PF-06647020 dose reduction/delay
Continue avelumab as per schedule
Grade 2
Delay PF-06647020 
until toxicity 
resolves to ANC 
1.0 x 109/L, then 
resume 
PF-06647020 (no 
dose reduction).**
Delay PF-06647020 until toxicity resolves to ANC 1.0 x 109/L, then 
resume PF-06647020 (no dose reduction).**  Continue avelumab as per 
schedule.
Grade 3  
Delay PF-06647020 
until toxicity 
resolves to ANC 
1.0 x 109/L, then 
resume 
PF-06647020 (no 
dose reduction).**
Delay PF-06647020 until toxicity resolves to ANC 1.0 x 109/L, resume 
PF-06647020 (no dose reduction).**
Continue avelumab as per schedule.
If Grade 3 toxicity recurs, delay PF-06647020 and avelumab until 
toxicity resolves to ANC 1.0 x 109/L, then resume PF-06647020 at 
reduced dose** and avelumab at standard dose.
If Grade 3 toxicity recurs with PF-06647020 at reduced dose, delay 
PF-06647020 until toxicity resolves to ANC 1.0 x 109/L, then resume 
PF-06647020 the reduced dose. ** 
For avelumab: 

If toxicity resolves to ANC 1.0 x 109/L, resume avelumab at the 
standard dose. 

If toxicity resolves to ANC 1.0 x 109/L, permanently discontinue 
avelumab.
Grade 4
Delay PF-06647020 
until toxicity 
resolves to ANC 
1.0 x 109/L, then 
resume PF-
06647020 at 
reduced dose level 
or continue at 
previous dose with 
prophylactic 
granulocyte growth 
factor support.**
Delay PF-06647020 and avelumab until toxicity resolves to Grade 1; 
then resume PF-06647020 at reduced dose level** and avelumab at 
standard dose.

If toxicity resolves to ANC 1.0 x 109/L, resume avelumab at the 
standard dose. 

If toxicity resolves to ANC 1.0 x 109/L, in >14 days, permanently 
discontinue avelumab.
** If hematological recovery is achieved within 14 days after the scheduled day of PF-06647020 treatment, 
resume PF-06647020 at the previous dose.  If hematological recovery is not achieved 14 days or more after 
the scheduled day of the course, the patient will permanently discontinue treatment unless discussed and 
agreed with the Sponsor.
A7.4. Investigational Product Storage 
The investigator or an approved representative, eg, pharmacist, will ensure that all 
investigational products, including PF-06647020 and avelumab, are stored in a secured area 
with controlled access under required storage conditions and in accordance with applicable 
regulatory requirements.


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
Avelumab must be stored in the refrigerator at 2-8C (36-46F).  Do not freeze.  
Protect from light.  Do not shake vigorously. 
Storage conditions stated in the SRSD (Investigator Brochure) will be superseded by storage 
conditions stated in the labeling.  
Refer to Section 5.5 for additional guidance.
A7.5. Surgery 
No formal studies of the effect of PF-06647020 or avelumab on wound healing have been 
conducted; however, caution is advised on theoretical grounds for any surgical procedures 
during the study.  
No surgical risk has been identified with immune checkpoint inhibitors.  No surgical 
precautions are mentioned in pembrolizumab, nivolumab or atezolizumab product labels.  If 
a major surgery or an interventional procedure (eg, endoscopy) is required, treatment with 
PF-06647020 or avelumab must be interrupted.  Patients may resume PF-06647020 or 
avelumab 2-3 weeks after major surgery, assuming the wound has completely healed and 
there are no wound healing complications (eg, delayed healing, wound infection or fistula).
Avelumab treatment does not need to be delayed for minor surgical procedures that do not 
involve general anesthesia. 
A8. DATA ANALYSIS/STATISTICAL METHODS
Refer to Section 9 of the main protocol for more details.


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Table A3. SCHEDULE OF ACTIVITIES: Single Agent Q2W Regimens  
Protocol Activities1
Screening2
Treatment Period
Post-Treatment 
Period
Cycle 1
Cycle 2
Cycle 3
Cycle 4+
EOT4
Follow 
up5
1 cycle = 4 weeks3
Day 1
Day 8
Day 15
Day 21
Day 1
Day 8
Day 15
Day 21
Day 1
Day 15
Day 1
Day 15
Visit Time Window (days)
(≤28)
(±1)
(±2)
(±2)
(±2)
(±2)
(±2)
(±2)
(±2)
(±2)
(±2)
(±2)
Informed Consent6
X
Tumor History7
X
Medical History
X
Ophthalmic Examination8
X
Height
X
Vital Signs9
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Physical Examination10
X
X
X
Abbreviated Physical Examination11
X
X
X
X
X
X
X
X
X
X
X
ECOG Performance Status12
X
X
X
X
X
X
Contraception Check13
X
X
X
X
X
Hematology14
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Blood Chemistry15
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Coagulation16
X
X
X
X
X
X
X
X
X
X
CA-12517
X
X
X
X
X
X
Urinalysis18
X
X
Pregnancy Test19
X
X
X
X
X
X
Single 12-lead ECG20
X
X
X
X
X
X
X
PK/ Immunogenicity/
Sampling
See Schedule of PK/Immunogenicity/Biomarker Assessment Table
Registration and Treatment
Registration21
X
PF-06647020 Administration22
X
X
X
X
X
X
X
X
Tumor Assessments
CT or MRI Scan23
X
X
Every 8 
weeks
X
Other Clinical Assessments
Adverse Events24
→
→
→
→
→
→
→
→
→
→
→
→
→
X
Concomitant Treatments25
→
→
→
→
→
→
→
→
→
→
→
→
X
Other Patient Samples
CCI
CCI


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Protocol Activities1
Screening2
Treatment Period
Post-Treatment 
Period
Cycle 1
Cycle 2
Cycle 3
Cycle 4+
EOT4
Follow 
up5
1 cycle = 4 weeks3
Day 1
Day 8
Day 15
Day 21
Day 1
Day 8
Day 15
Day 21
Day 1
Day 15
Day 1
Day 15
Visit Time Window (days)
(≤28)
(±1)
(±2)
(±2)
(±2)
(±2)
(±2)
(±2)
(±2)
(±2)
(±2)
(±2)
 
Abbreviations: CT = computed tomography; ECG = electrocardiogram; EOT = end of treatment; 
; LVEF = left ventricular ejection 
fraction; MRI = magnetic resonance imaging; BP = blood pressure; PR = pulse rates; PK = pharmacokinetics; ECOG = Eastern Cooperative Oncology Group; OVCA = Ovarian 
cancer
Unless otherwise specified, laboratory values and assessments should be obtained prior to study treatment.  If the infusion is held, assessments should still be performed. 
Footnotes 
1.
Protocol Activities: All assessments should be performed prior to dosing with study medication unless otherwise specified.  There is no need to repeat activity at Day 1 if it 
was done during the screening timeframe of 28 days unless otherwise specified.
2.
Screening: All assessments to be performed within 28 days prior to randomization. Consent may be obtained >28 days.
3.
Study Cycle: Cycle length is 4 weeks for each treatment arm. 
4.
End of Treatment/Withdrawal: Obtain these assessments if not completed within the prior week, except for tumor assessments, which need not be repeated if performed 
within the prior 4 weeks. 
5.
Follow-up: At least 28 days and no more than 35 days after end of treatment visit, patients will return to undergo review of concomitant medications, vital signs, and 
assessment for resolution of any treatment related toxicity.  Patients continuing to experience toxicity at this point following discontinuation of treatment will continue to be 
followed at least every 4 weeks until resolution or determination, in the clinical judgment of the Investigator, that no further improvement is expected.
6.
Informed Consent: Must be obtained prior to undergoing any study-specific procedures.
7.
Tumor History: Includes collection of tumor history, prior anti-tumor regimen(s), including treatment duration and best response observed.
8.
Ophthalmic Examination:  An eye exam (performed by an ophthalmologist) will be performed at screening.  The eye exam includes Best Corrected Visual Acuity (BCVA), 
Intraocular Pressure (IOP) preferably by Goldmann applanation, Biomicroscopic Exam (also called slit lamp exam) to evaluate the Lids/Lashes/Adnexae, conjunctiva/sclera, 
cornea, anterior chamber, iris, lens, and Dilate fundus exam to evaluate the optic nerve, the vessels, the macula, and the peripheral retina.  Further ophthalmic examinations 
should be guided by specific ocular signs and symptoms should they occur during treatment and follow up.
9.
Vital Signs: Blood pressure (BP) and pulse rate should be taken before any other assessments (eg, PK, laboratory blood draws) with the patient in the seated position after the 
patient has been sitting quietly for at least 5 minutes.  
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10. Physical Examination: Includes an examination of major body systems, and weight (height included at screening only).  Abnormal findings identified prior to first dose of 
study treatment should be documented on the Medical History CRF page.
11. Abbreviated Physical Exam: Should be performed as appropriate at each visit where full physical exams are not required, and on an as needed basis for assessment of AEs.  
Abbreviated exams should be targeted to specific symptoms or complaints and be consistent with local standard of care. 
12. ECOG Performance status: Use Eastern Cooperative Oncology Group (ECOG).
13. Contraception Check: Patients who are of childbearing potential will need to affirm that they meet the criteria for correct use of 2 of the selected methods of contraception.  
The investigator or his or her designee will discuss with the patient the need to use 2 highly effective contraception methods consistently and correctly 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 one or both selected contraception 
methods are discontinued, or if pregnancy is known or suspected in the patient.
14. Hematology: No need to repeat on C1D1 if screening assessment performed within 7 days prior to that date.  See Assessments section in main body of protocol for 
Laboratory Tests list. Results should be available for review prior to infusion of treatment. 
15. Blood Chemistry: No need to repeat on C1D1 if screening assessment performed within 7 days prior to that date.  See Assessments section in main body of protocol for 
Laboratory Tests list. Results should be available for review prior to infusion of treatment. 
16. Coagulation: No need to repeat on C1D1 if baseline assessment performed within 7 days prior to that date.  See Assessments section in main body of protocol for Laboratory 
Tests list.  
17. CA-125: Will be assessed locally according to the schedule in the table. 
18. Urinalysis: Dipstick is acceptable.  Microscopic analyses must be performed if dipstick is abnormal. 
19. Serum/Urine Pregnancy Test: For female patients of childbearing potential, a urine or serum pregnancy test, with sensitivity of at least 25 mIU/mL, will be performed on 
two occasions prior to starting study treatment, once at the start of screening and once at the baseline visit, immediately before study treatment administration.  Urine 
pregnancy tests will also be routinely repeated at every treatment cycle during the active treatment period, at the end of study therapy and additionally whenever one 
menstrual cycle is missed or when potential pregnancy is otherwise suspected.  Additional pregnancy tests may also be undertaken if requested by institutional review 
board/ethics committee (IRB/ECs) or if required by local regulations.  See Section 7.1.1 for contraception guidelines.
20. 12-Lead ECGs: ECG measurement will be collected during screening and at the End of Treatment Visit.  On-treatment ECGs will be performed on Day 1 of Cycles 1, 2, and 
3 and Day 15 of Cycle 1 (all pre-infusion).  In Cycle 4 and subsequent cycles, a single ECG should be taken pre-dose on Day 1.  When coinciding with blood sample draws 
for pharmacokinetics (PK), ECG assessment should be performed prior to blood sample collection, such that the blood sample is collected at the nominal time.  It is 
recommended that ECGs are performed prior to any blood collection or other invasive procedures.  If patient experiences a cardiac or neurologic AE (specifically syncope, 
dizziness, seizures, or stroke) triplicate ECGs should be obtained at time of the event.  If the mean QTcF is prolonged (>500 msec), the ECGs should be re-evaluated by a 
qualified person at the institution for confirmation and repeated as clinically indicated.  Additional triplicate ECGs may be performed as clinically indicated (see 
Section 7.1.5). Beginning at Cycle 8, the Day 8 assessments will be optional for patients that have achieved a CR, PR or SD if agreed upon by the treating physician.
21. Registration: Patient number and dose level allocation will be provided by Pfizer Inc.
22. Study Treatment: PF-06647020 will be given as a 1-hour intravenous infusion (IV) every 2 weeks.  Weight should be collected prior to each infusion, assessed and 
documented in the CRF.  
23. Tumor Assessments: Tumor assessments will include all known or suspected disease sites.  Tumor assessments must include chest, abdomen and pelvis CT or MRI scans 
and will be conducted every 8 weeks (window of 5 days prior to dosing is allowed) from the start of study treatment until disease progression by RECIST (v1.1) or death, or 


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at the time of withdrawal from treatment (if not done in previous 8 weeks). If PR or CR is observed and the response duration exceeded 6 months, tumor assessment can be 
assessed at a 12-week interval. Brain scans will be performed at baseline only if disease is suspected and on study as appropriate to follow disease.  Baseline central nervous 
system (CNS) imaging is not required with the exception of symptomatic patients to rule out CNS metastases.  A bone scan (bone scintigraphy) or 18FDG-PET/CT is required 
at baseline only if disease is suspected and then every 16 weeks only if bone metastases are present at baseline.  Otherwise, bone imaging is required only if new bone 
metastases are suspected.  Bone imaging is also required at the time of CR confirmation for patients who have bone metastases.  MRI is acceptable for bone imaging if 
consistent with local practice.  Responses of complete response (CR) or partial response (PR) must be confirmed by repeat assessment no less than 4 weeks after the criteria 
for response are first met. All radiographic images will be collected for potential central review. Additional information on diagnostic imaging procedures and collection will 
be included in the Imaging Manual.
24. Adverse Event (AE) Assessments: AEs should be documented and recorded in the CRF.  The National Cancer Institute Common Terminology Criteria for Adverse Events 
(NCI CTCAE) version (v) 4.03 will be used. The time period for actively eliciting and collecting AEs and SAEs (“active collection period”) for each patient begins from the 
time the patient provides informed consent through and including a minimum of 28 calendar days after the last investigational product administration.  If the patient begins a 
new anticancer therapy, the period for recording non-serious AEs on the CRF ends at the time the new treatment is started.  However, any SAEs occurring during the active 
collection period must still be reported to Pfizer Safety and recorded on the CRF, irrespective of any intervening treatment. See Section 8.1.1.
25. Concomitant Treatments: All concomitant medications and Non-Drug Supportive Interventions should be recorded in the CRF.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table A4. SCHEDULE OF ACTIVITIES: Pharmacokinetic, Immunogenicity, and Biomarker Sampling Schedule (Single 
Agent and Combination PF-06647020 with Avelumab Q2W Regimen)
Protocol Activity
Cycle 1
Cycle 2
Cycle 3
Cycles 
≥4
EOT/
Withdrawal 
Visit
Safety 
Follow-up
1 cycle = 4 weeks
Day 1
Day 2
Day 4 Day 8 
Day 15
Day 1
Day 15 
Day 1
Day
2
Day 4 Day 8 
Day
15 
Day 1
Visit Window 
(days)
(±1)
(±1)
(±2)
(±2)
(±1)
(±1)
(±2)
Pre-
dose*
EOI
*
4 hr* 24 hr*
Pre-
dose*
EOI
*
Pre-
dose*
EOI
*
Pre-
dose*
EOI
*
Pre-
dose*
EOI
*
4 hr* 24 hr*
Pre-
dose*
EOI
*
Pre-
dose*
PK Sampling for 
PF-06647020 and 
hu6M024 mAb1
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
PK Sampling for 
PF-063801012
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
PK Sampling for 
Avelumab 
(avelumab 
combination 
cohort only)3
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
 
Blood Sample for 
Immunogenicity 
Test (Anti-PF-
06647020)5
X
X
X
X
X
X
X
Blood Sampling 
for 
Immunogenicity 
Test (Anti-
avelumab, 
avelumab 
combination 
cohort only)6
X
X
X
X
X
X
X
Immune Cell 
Phenotyping (all 
Part 1 and OVCA 
cohorts in Part 27
X
X
X
X
RNA Analysis8
X
X
X
X
X
X
X
X (cycle 
5 only)
X
Cytokines/
Chemokines9
X
X
X
X
X
X
X
X (cycle 
5 only)
X
Whole Blood for 
DNA Analysis10
X
X
X
X
X (cycle 
5 only)
X
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Abbreviations: EOI = end of infusion; EOT = end of treatment; PK = pharmacokinetics, mAb = monoclonal antibody; OVCA = ovarian cancer; RNA = ribonucleic acid; 
DNA = deoxyribonucleic acid
* Sampling times are related to the start of infusion; all samples obtained within 10% of the nominal time (eg, within 6 minutes of a 60 minute sample) will be 
considered protocol compliant, and the exact time of the sample collection will always be noted on the CRF.
Footnotes 
1.
PK Sampling for PF-06647020 and hu6M024 mAb: Blood samples (6 mL) for PF-06647020 and hu6M024 mAb PK will be collected in all patients: pre-PF-06647020 
dose, at the end of PF-06647020 infusion (immediately before the end of infusion), and 4 hours of Day 1, Day 2 (24 hours), Days 4, 8, and 15 (pre-PF-06647020 dose and at 
the end of PF-06647020 infusion) of Cycles 1 and 3; Pre-PF-06647020 dose and at the end of PF-06647020 infusion on Days 1 and 15 of Cycle 2; pre-PF-06647020 dose on 
Day 1 of Cycles 4 and beyond, at the End of Treatment and at Day 30 Safety Follow-up visit.  
2.
PK Sampling for PF-06380101: Blood samples (4 mL) for PF-06380101 PK will be collected in all patients: pre-PF-0067020 dose, at the end of PF-06647020 infusion 
(immediately before the end of infusion), and 4 hours of Day 1, Day 2 (24 hours), Days 4, 8, and 15 (pre-PF-06647020 dose and at the end of infusion) of Cycles 1 and 3; 
Pre-PF-06647020 dose and at the end of PF-06647020 infusion on Days 1 and 15 of Cycle 2; pre-PF-06647020 dose on Day 1 of Cycles 4 and beyond, at the End of 
Treatment and at Day 30 Safety Follow-up visit.  
3.
PK Sampling for Avelumab: Blood samples (4 mL) for avelumab PK will be collected in all avelumab combination cohort patients: pre-avelumab dose, at the end of 
avelumab infusion (immediately before the end of infusion), and 4 hours of Day 1, Day 2 (24 hours), Days 4, 8, and 15 (pre-avelumab dose and at the end of infusion) of 
Cycles 1 and 3; Pre-avelumab dose and at the end of avelumab infusion on Days 1 and 15 of Cycle 2; pre-avelumab dose on Day 1 of Cycles 4 and beyond, at the End of 
Treatment and at Day 30 Safety Follow-up visit.
 
5.
Blood Sample for PF-06647020 Immunogenicity Test: Blood samples (6 mL) for immunogenicity testing against PF-06647020 will be collected in all patients at baseline 
(2 hours before the start of PF-6647020 infusion on Day 1 of Cycle 1), pre-dose (prior to PF-06647020 infusion) on Day 15 of Cycle 1, and pre-dose (prior to PF-06647020 
infusion) on Day 1 of Cycles 2 and beyond and at the End of Treatment.  An additional sample for immunogenicity must be collected at 30 days after the last dose of 
PF-06647020.  
6.
Blood Sample for avelumab Immunogenicity Test: Blood samples (3.5 mL) for immunogenicity testing against avelumab will be collected in all avelumab combination 
cohort patients at baseline (2 hours before the start of PF-6647020 infusion on Day 1 of Cycle 1), pre-dose (prior to PF-06647020 infusion) on Day 15 of Cycle 1, and 
pre-dose (prior to PF-06647020 infusion) on Day 1 of Cycles 2 and beyond and at the End of Treatment.  An additional sample for immunogenicity must be collected at 
30 days after the last dose of avelumab.  
7.
Immune Cell Phenotyping:  A 4 mL whole blood sample will be collected in a K2EDTA tube at Cycle 1 Day 1 (pre-dose) and Day 8, and Cycle 2 Day 15 (pre-dose), and at 
End of Treatment from all patients in Part 1 and from patients in the following Part 2 cohorts 1) with platinum resistant or refractory OVCA  treated with single agent 
PF-06647020; 2) platinum resistant or refractory OVCA treated with PF-06647020 in combination with avelumab. Immune cell functional markers will be measured by flow 
cytometry.
8.
RNA analysis: A 2.5 mL whole blood sample will be collected into PAXgene (RNA) tubes at Cycle 1 Day 1 (pre-dose) and end of infusion (EOI) of the last investigational 
product (IP) administered, and on Cycle 1 Day 4, Day 8 and Day 15, and Cycle 2 Day 1 and Day 15, and Cycle 5 Day 1, and End of Treatment.  RNA may be analyzed for 
expression profile of immune- and tumor-related transcripts.
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9.
Cytokines/Chemokines: A 4 mL blood sample will be collected into serum collection tubes at Cycle 1 Day 1 (pre-dose) and end of infusion (EOI) of the last investigational 
product (IP) administered, and on Cycle 1 Day 4, Day 8 and Day 15, and Cycle 2 Day 1, Cycle 3 Day 1, Cycle 5 Day 1 and End of Treatment.  Samples may be analyzed for 
soluble factors associated with immune activation, regulation and potential pharmacodynamic activity of PF-06647020.   
10. Whole Blood for DNA Analysis: A 4 mL whole blood sample will be collected in a tube optimized for deoxyribonucleic acid (DNA) preservation at Cycle 1 Day 1 
(pre-dose), and Day 15 (pre-dose), Cycle 2 Day 1 (pre-dose), Cycle 3 Day 1 (pre-dose), Cycle 5 Day 1 (pre-dose) and End of Treatment.  DNA may be submitted for TCR 
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Table A5. SCHEDULE OF ACTIVITIES: Combination PF-06647020 with Avelumab Q2W Regimen  
Protocol Activities1
Screening2
Treatment Period
Post-Treatment 
Period
Cycle 1
Cycle 2
Cycle 3
Cycle 4+
1 cycle = 4 weeks3
EOT4 Follow 
up5
Day 1
Day 8
Day 15
Day 21
Day 1
Day 8
Day 15
Day 21
Day 1
Day 15
Day 1
Day 15
Visit Time Window (days)
(≤28)
(±1)
(±2)
(±2)
(±2)
(±2)
(±2)
(±2)
(±2)
(±2)
(±2)
(±2)
Informed Consent6
X
Tumor History7
X
Medical History
X
Ophthalmic Examination8
X
Height
X
Vital Signs9
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Physical Examination10
X
X
X
Abbreviated Physical Examination11
X
X
X
X
X
X
X
X
X
X
X
ECOG Performance Status12
X
X
X
X
X
X
Contraception Check13
X
X
X
X
X
Hematology14
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Blood Chemistry15
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Coagulation16
X
X
X
X
X
X
X
X
X
X
ACTH, Free T4, TSH17
X
X
X
X
HBV, HCV18
X
ANA, ANCA, RF
X
CA-12519
X
X
X
X
X
X
BRCA 1/2 Mutation Status20
X
Urinalysis21
X
X
Pregnancy Test22
X
X
X
X
X
X
Triplicate/Single 12-lead ECG23
X
X
X
X
X
X
X
PK/Immunogenicity/
Sampling
See Schedule of PK/Immunogenicity/Biomarker Assessment Table
Registration and Treatment
Registration24
X
PF-06647020 + avelumab 
Administration25
X
X
X
X
X
X
X
X
Tumor Assessments
CT or MRI Scan26
X
X
Every 8 
weeks
X
Other Clinical Assessments
Adverse Events27
→
→
→
→
→
→
→
→
→
→
→
→
→
X
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Protocol Activities1
Screening2
Treatment Period
Post-Treatment 
Period
Cycle 1
Cycle 2
Cycle 3
Cycle 4+
1 cycle = 4 weeks3
EOT4 Follow 
up5
Day 1
Day 8
Day 15
Day 21
Day 1
Day 8
Day 15
Day 21
Day 1
Day 15
Day 1
Day 15
Visit Time Window (days)
(≤28)
(±1)
(±2)
(±2)
(±2)
(±2)
(±2)
(±2)
(±2)
(±2)
(±2)
(±2)
Concomitant Treatments28
→
→
→
→
→
→
→
→
→
→
→
→
X
Other Patient Samples
Abbreviations: CT = computed tomography; ECG = electrocardiogram; EOT = end of treatment; 
; LVEF = left ventricular ejection 
fraction; MRI = magnetic resonance imaging; BP = blood pressure; PR = pulse rates; PK = pharmacokinetics; ECOG = Eastern Cooperative Oncology Group; OVCA = Ovarian 
cancer; ACTH = adrenocorticotropic hormone; TSH = thyroid stimulating hormone; HBV = Hepatitis B virus; HCV = Hepatitis C virus; ANA = antinuclear antibody; ANCA = 
anti-neutrophil cytoplasmic antibodies; RF = rheumatoid factor
Unless otherwise specified, laboratory values and assessments should be obtained prior to study treatment.  If the infusion is held, assessments should still be performed.  
Footnotes 
1.
Protocol Activities: All assessments should be performed prior to dosing with study medication unless otherwise specified.  There is no need to repeat activity at Day 1 if it 
was done during the screening timeframe of 28 days unless otherwise specified.
2.
Screening: All assessments to be performed within 28 days prior to randomization. Consent may be obtained >28 days.
3.
Study Cycle: Cycle length is 4 weeks for each treatment arm. 
4.
End of Treatment/Withdrawal: Obtain these assessments if not completed within the prior week, except for tumor assessments, which need not be repeated if performed 
within the prior 4 weeks. 
5.
Follow-up: At least 28 days and no more than 35 days after end of treatment visit, patients will return to undergo review of concomitant medications, vital signs, and 
assessment for resolution of any treatment related toxicity.  Patients continuing to experience toxicity at this point following discontinuation of treatment will continue to be 
followed at least every 4 weeks until resolution or determination, in the clinical judgment of the Investigator, that no further improvement is expected. 
6.
Informed Consent: Must be obtained prior to undergoing any study-specific procedures.
7.
Tumor History: Includes collection of tumor history, prior anti-tumor regimen(s), including treatment duration and best response observed.
8.
Ophthalmic Examination:  An eye exam (performed by an ophthalmologist) will be performed at screening.  The eye exam includes Best Corrected Visual Acuity (BCVA), 
Intraocular Pressure (IOP) preferably by Goldmann applanation, Biomicroscopic Exam (also called slit lamp exam) to evaluate the Lids/Lashes/Adnexae, conjunctiva/sclera, 
cornea, anterior chamber, iris, lens, and Dilate fundus exam to evaluate the optic nerve, the vessels, the macula, and the peripheral retina.  Further ophthalmic examinations 
should be guided by specific ocular signs and symptoms should they occur during treatment and follow up.
9.
Vital Signs: Blood pressure (BP) and pulse rate should be taken before any other assessments (eg, PK, laboratory blood draws) with the patient in the seated position after the 
patient has been sitting quietly for at least 5 minutes.  
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10. Physical Examination: Includes an examination of major body systems, and weight (height included at screening only).  Abnormal findings identified prior to first dose of 
study treatment should be documented on the Medical History CRF page.
11. Abbreviated Physical Exam: Should be performed as appropriate at each visit where full physical exams are not required, and on an as needed basis for assessment of AEs.  
Abbreviated exams should be targeted to specific symptoms or complaints and be consistent with local standard of care. 
12. ECOG Performance status: Use Eastern Cooperative Oncology Group (ECOG).
13. Contraception Check: Patients who are of childbearing potential will need to affirm that they meet the criteria for correct use of 2 of the selected methods of contraception.  
The investigator or his or her designee will discuss with the patient the need to use 2 highly effective contraception methods consistently and correctly 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 one or both selected contraception 
methods are discontinued, or if pregnancy is known or suspected in the patient.
14. Hematology: No need to repeat on C1D1 if screening assessment performed within 7 days prior to that date.  See Assessments section in main body of protocol for 
Laboratory Tests list. Results should be available for review prior to infusion of treatment. 
15. Blood Chemistry: No need to repeat on C1D1 if screening assessment performed within 7 days prior to that date.  See Assessments section in main body of protocol for 
Laboratory Tests list. Results should be available for review prior to infusion of treatment. 
16. Coagulation: No need to repeat on C1D1 if baseline assessment performed within 7 days prior to that date.  See Assessments section in main body of protocol for Laboratory 
Tests list.
17. ACTH and Thyroid Function Tests: ACTH, Free T4 and TSH will be measured prior to trial treatment, every 8 weeks for 2 additional measurements, then every 12 weeks 
thereafter while on treatment, End of Treatment, and as clinically indicated. 
18. HBV serology and HCV serology: measured prior to study enrollment and then as clinically indicated.
19. CA-125: Will be assessed locally according to the schedule in the table. 
20. BRCA status: If BRCA1/2 mutation status is known or becomes known for a patient during the study, this information will be recorded in the CRF either at screening or at 
later visits.  No BRCA1/2 testing is required for this study.
21. Urinalysis: Dipstick is acceptable.  Microscopic analyses must be performed if dipstick is abnormal. 
22. Serum/Urine Pregnancy Test: For female patients of childbearing potential, a urine or serum pregnancy test, with sensitivity of at least 25 mIU/mL, will be performed on 
two occasions prior to starting study treatment, once at the start of screening and once at the baseline visit, immediately before study treatment administration.  Urine 
pregnancy tests will also be routinely repeated at every treatment cycle during the active treatment period, at the end of study therapy and additionally whenever one 
menstrual cycle is missed or when potential pregnancy is otherwise suspected.  Additional pregnancy tests may also be undertaken if requested by institutional review 
board/ethics committee (IRB/ECs) or if required by local regulations.  
23. 12-Lead ECGs: All patients require a triplicate ECG measurement at screening.  On-treatment ECGs will be performed on Day 1 of Cycles 1, 2, and 3 and Day 15 of Cycle 1
(all at pre-infusion).  At each time point, three (3) consecutive 12-lead ECGs (triplicates) will be performed approximately 2 minutes apart (within 10 minutes) to determine 
mean QTc (average of triplicates).  In Cycle 4 and subsequent cycles, a single ECG should be taken pre-dose on Day 1.  When coinciding with blood sample draws for 
pharmacokinetics (PK), ECG assessment should be performed prior to blood sample collection, such that the blood sample is collected at the nominal time.  It is 
recommended that ECGs are performed prior to any blood collection or other invasive procedures.  If patient experiences a cardiac or neurologic AE (specifically syncope, 
dizziness, seizures, or stroke) triplicate ECGs should be obtained at time of the event.  If the mean QTcF is prolonged (>500 msec), the ECGs should be re-evaluated by a 
qualified person at the institution for confirmation and repeated as clinically indicated.  Additional triplicate ECGs may be performed as clinically indicated. 
24. Registration: Patient number and dose level allocation will be provided by Pfizer Inc.


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25. Study Treatment: PF-06647020 will be given as a 1-hour intravenous infusion (IV) followed by avelumab given as a 1-hour intravenous infusion every 2 weeks.  Weight 
should be collected prior to each infusion, assessed and documented in the CRF.  There is a plus or minus 3 day window for PF-06647020 and avelumab administration, but 
there should be no less than 10 days between next PF-06647020 and avelumab doses.  For additional information about premedications see Section A7.2.2.1.
26. Tumor Assessments: Tumor assessments will include all known or suspected disease sites.  Tumor assessments must include chest, abdomen and pelvis CT or MRI scans 
and will be conducted every 8 weeks (window of 5 days prior to dosing is allowed) from the start of study treatment until disease progression by RECIST (v1.1) or death, or 
at the time of withdrawal from treatment (if not done in previous 8 weeks). If PR or CR is observed and the response duration exceeded 6 months, tumor assessment can be 
assessed at a 12-week interval. Brain scans will be performed at baseline only if disease is suspected and on study as appropriate to follow disease.  Baseline central nervous 
system (CNS) imaging is not required with the exception of symptomatic patients to rule out CNS metastases.  A bone scan (bone scintigraphy) or 18FDG-PET/CT is required 
at baseline only if disease is suspected and then every 16 weeks only if bone metastases are present at baseline.  Otherwise, bone imaging is required only if new bone 
metastases are suspected.  Bone imaging is also required at the time of CR confirmation for patients who have bone metastases.  MRI is acceptable for bone imaging if 
consistent with local practice.  Responses of complete response (CR) or partial response (PR) must be confirmed by repeat assessment no less than 4 weeks after the criteria 
for response are first met. All radiographic images will be collected for potential central review. Additional information on diagnostic imaging procedures and collection will 
be included in the Imaging Manual.
27. Adverse Event (AE) Assessments: AEs should be documented and recorded in the CRF.  The NCI CTCAE version 4.03 will be used.  The time period for actively eliciting 
and collecting AEs and SAEs (“active collection period”) for each patient begins from the time the patient provides informed consent through and including a minimum of 
28 calendar days after the last investigational product administration.  If the patient begins a new anticancer therapy, the period for recording non serious AEs on the CRF 
ends at the time the new treatment is started.  However, any SAEs occurring during the active collection period must still be reported to Pfizer Safety and recorded on the 
CRF, irrespective of any intervening treatment.  See Section 8.1.1.
28. Concomitant Treatments: All concomitant medications and Non-Drug Supportive Interventions should be recorded in the CRF.   
 
 
 
 
 
 
 
 
 
 
 
 
 
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Appendix 9. Immune-related Response Criteria Derived from RECIST 1.1 (irRECIST)
Increasing clinical experience indicates that traditional response criteria may not be sufficient 
to fully characterize activity in this new era of targeted therapies and/or biologics.  
This is particularly true for immunotherapeutic agents such as anti-CTLA4 and anti-PD1\anti 
PDL1 which exert the anti-tumor activity by augmenting activation and proliferation of 
T cells, thus leading to tumor infiltration by T cells and tumor regression rather than direct 
cytotoxic effects.24,25  Clinical observations of patients with advanced melanoma treated with 
ipilimumab, for example, suggested that conventional response assessment criteria such as 
Response Evaluation Criteria in Solid Tumors (RECIST) and World Health Organization 
(WHO) criteria are not sufficient to fully characterize patterns of tumor response to
immunotherapy because tumors treated with immunotherapeutic agents may show additional 
response patterns that are not described in these conventional criteria.26,27
Furthermore, the conventional tumor assessment criteria (RECIST and WHO criteria) have 
been reported as not capturing the existence of a subset of patients who have an OS similar to 
those who have experienced CR or PR but were flagged as PD by WHO criteria.26,27
On these grounds, a tumor assessment system has been developed that incorporates these 
delayed or flare-type responses into the RECIST 1.1 criteria (irRECIST).28
For irRECIST, only target and new measurable lesions are taken into account.  In contrast to 
the RECIST 1.1, the irRECIST criteria.

require confirmation of both progression and response by imaging at least 4 weeks 
from the date first documented, and 

does not necessarily score the appearance of new lesions as progressive disease if the 
sum of lesion diameters of target lesions (minimum of 10 mm per lesion, maximum 
of 5 target lesions, maximum of 2 per organ) and measurable new lesions does not 
increase by 20%. 
The same method of assessment and the same technique should be used to characterize each 
identified and reported target lesion(s) at baseline and throughout the trial.
irRECIST criteria are defined as follows: 

Overall immune-related complete response (irCR): Complete disappearance of all 
lesions (whether measurable or not) and no new lesions.  All measurable lymph nodes 
also must have a reduction in short axis to <10 mm. 

Overall immune-related partial response (irPR): Sum of the diameters (longest for 
non-nodal lesions, shortest for nodal lesions) of target and new measurable lesions 
decreases 30%. 


PF-06647020
B7661001
Final Protocol Amendment 8, 09 November 2017
Page 194

Overall immune-related stable disease (irSD): Sum of the diameters (longest for 
non-nodal lesions, shortest for nodal lesions) of target and new measurable lesions 
neither irCR, irPR, (compared to baseline) or immune-related progressive disease 
(irPD, compared to nadir). 

Overall immune-related progressive disease (irPD): Sum of the diameters (longest for 
non-nodal lesions, shortest for nodal lesions) of target and new measurable lesions 
increases 20% (compared to nadir), confirmed by a repeat, consecutive observation 
at least 4 weeks from the date first documented. 
New measurable lesions: Incorporated into tumor burden (ie, added to the target lesion 
measurements).  A lymph node has to be 15 mm in short axis to be a measurable new lesion 
and its short axis measurement is included in the sum. Up to 2 new lesions per organ and up 
to 5 new lesions in total can be added to the measurements. 
New non-measurable lesions: Do not define progression but preclude irCR.
Overall responses derived from changes in index, non-index, and new lesions are outlines in 
Table 23.
Table 23.
Overall Response Derived from Changes in Index, Non-index and New 
Lesions
Measurable response
Non-measurable response
Overall response using 
irRECISTb
Index and New 
Measurable Lesions 
(Tumor Burden)a
Non-Index Lesions
New, nonmeasurable 
Lesions
Decrease 100%
Absent
Absent
irCR
Decrease 100%
Stable
Any
irPR
Decrease 100%
Unequivocal progression
Any
irPR
Decrease 30%
Absent/stable
Any
irPR
Decrease 30%
Unequivocal progression
Any
irPR
Decrease <30% and 
increase <20%
Absent/stable
Any
irSD
Decrease <30% and 
increase <20%
Unequivocal progression
Any
irSD
Increase 20%
Any
Any
irPD
a.
Decrease assessed relative to baseline.
b.
Response (irCR and irPR) and progression (irPD) must be confirmed by a second, consecutive 
assessment at least 4 weeks apart.

SAP_001.pdf: 
Protocol B7661001 (PF-06647020)
Statistical Analysis Plan Amendment 1
04DEC2018
Page 1
Protocol B7661001
A FIRST-IN-HUMAN PHASE 1, DOSE ESCALATION, SAFETY AND
PHARMACOKINETIC STUDY OF PF-06647020 IN ADULT PATIENTS WITH
ADVANCED SOLID TUMORS
Statistical Analysis Plan Amendment
(SAP)
Version: Amendment 1
Author:
 (the last Final version authored by 
)
Date:
04-DEC-2018
PPD
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Protocol B7661001 (PF-06647020)
Statistical Analysis Plan Amendment 1
04DEC2018
Page 2
TABLE OF CONTENTS
LIST OF TABLES.....................................................................................................................4
1. AMENDMENTS FROM PREVIOUS VERSION(S) ...........................................................9
2. INTRODUCTION .................................................................................................................9
2.1. Study Design .............................................................................................................9
2.2. Study Objectives .....................................................................................................10
2.2.1. Dose Escalation (Part 1) Objectives ...........................................................10
2.2.1.1. Primary Objectives....................................................................10
2.2.1.2. Secondary Objectives................................................................10
..............................................................11
2.2.2. Dose Expansion (Part 2) Objectives...........................................................11
2.2.2.1. Primary Objectives....................................................................11
2.2.2.2. Secondary Objectives................................................................11
..............................................................11
2.2.3. Objectives for Q2W Regimen ....................................................................12
2.2.3.1. Primary Objectives....................................................................12
2.2.3.2. Secondary Objectives................................................................12
..............................................................12
3. INTERIM ANALYSES, FINAL ANALYSES AND UNBLINDING................................13
4. HYPOTHESES AND DECISION RULES.........................................................................13
4.1. Statistical Hypotheses .............................................................................................13
4.2. Statistical Decision Rules........................................................................................13
5. ANALYSIS SETS ...............................................................................................................13
5.1. Full Analysis Set .....................................................................................................13
5.2. ‘PER PROTOCOL’ Analysis Set Evaluable for MTD ...........................................13
5.3. Safety Analysis Set..................................................................................................14
5.4. OTHER ANALYSIS SETS ....................................................................................14
5.4.1. PK Concentration Analysis Set ..................................................................14
5.4.2. PK Parameter Analysis Set.........................................................................14
.........................................................................14
5.4.4. Immunogenicity Analysis Set.....................................................................14
........................................................................14
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Statistical Analysis Plan Amendment 1
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5.4.6. Drug-Drug Interaction (DDI) Study Analysis Set......................................14
5.5. Treatment Misallocations........................................................................................15
5.6. Protocol Deviations.................................................................................................15
5.6.1. Deviations Assessed Orior to Randomization............................................15
5.6.2. Deviations Assessed Post-Randomization..................................................15
6. ENDPOINTS AND COVARIATES ...................................................................................15
6.1. Efficacy Endpoints ..................................................................................................15
6.2. Safety Endpoints .....................................................................................................16
.............................................................................................16
6.4. Pharmacokinetics Endpoints ...................................................................................17
6.5. PD Endpoint ............................................................................................................18
6.6. Immunogenicity Endpoints .....................................................................................18
6.6.1. Outcomes Research Endpoints ...................................................................18
6.7. Covariates................................................................................................................18
7. HANDLING OF MISSING VALUES ................................................................................18
8. STATISTICAL METHODOLOGY AND STATISTICAL ANALYSES ..........................18
8.1. Statistical Methods ..................................................................................................18
8.1.1. Analyses for Continuous Data....................................................................18
8.1.2. Analyses for Categorical Data....................................................................18
8.1.3. Analyses for Binary endpoints....................................................................19
8.1.4. Analyses for Time-to-Event Data...............................................................19
8.2. Statistical Analyses .................................................................................................19
8.2.1. Primary Analysis ........................................................................................19
8.2.2. Efficacy Analyses .......................................................................................19
8.2.2.1. Progression-Free Survival (PFS) ...............................................19
8.2.2.2. Time to progression (TTP)........................................................21
8.2.2.3. Duration of Response (DoR).....................................................23
8.2.2.4. Overall Response Rate (ORR) ..................................................23
8.2.2.5. Disease Control Rate (DCR).....................................................25
8.2.2.6. Clinical Benefit Response (CBR) .............................................25
8.2.3. Safety Analyses ..........................................................................................25
8.2.4. Other Safety Data – Screening and Other Special Purpose Data ...............28
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Statistical Analysis Plan Amendment 1
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Page 4
8.2.5. PK Analyses................................................................................................29
8.2.5.1. Concentrations below the Limit of Quantification....................29
8.2.5.2. Deviations, Missing Concentrations and Anomalous 
Values................................................................................................29
8.2.5.3. Pharmacokinetic Parameters .....................................................29
8.2.6. Drug-Drug Interaction Analysis (DDI sub-study only)..............................31
................................................................................32
9. REFERENCES ....................................................................................................................33
LIST OF TABLES
Table 1.
Decision Rules......................................................................................................13
Table 2.
PFS Outcome and Event Dates.............................................................................20
Table 3.
PFS Censoring Reasons and Hierarchy................................................................21
Table 4.
TTP Outcome and Event Dates ............................................................................22
Table 5.
TTP Censoring Reasons and Hierarchy................................................................22
Table 6.
Derivation of Best Overall Response When Confirmation Of Response Is 
Required................................................................................................................24
Table 7.
Scenarios of Assignments of Best Overall Response using irRECIST................25
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Statistical Analysis Plan Amendment 1
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Page 5
Abbreviation
Term
ADA
Anti-drug Antibody
ADC
Antibody Drug Conjugate
ADCC
Antibody dependent cell mediated cytotoxicity
AE
Adverse Event
AIDS
Acquired Immunodeficiency Syndrome
ALK
Anaplastic Lymphoma Kinase
ALT
Alanine Aminotransferase
AML
Acute Myeloid Leukemia
ANC
Absolute Neutrophil Count
ASCO
American Society of Clinical Oncology
AST
Aspartate Aminotransferase
AUC
Area Under the Concentration-Time Curve
BP
Blood Pressure
C1D1
Cycle 1 Day 1
CBC
Complete Blood Count
CBR
Clinical Benefit Response
CDC
Complement Mediated Cytotoxicity
CL
Systemic Clearance
CNS
Central Nervous System
CR
Complete Response
CSC
Cancer Stem Cells
CSR
Clinical Study Report
CT
Computed Tomography
CTC
Circulating Tumor Cells
CTCAE
Common Terminology Criteria for Adverse Events
DAI
Dosage Administration Instruction
DAR
Drug:mAb Ratio
DDI
Drug-Drug-Interaction
DLT
Dose Limiting Toxicities


Protocol B7661001 (PF-06647020)
Statistical Analysis Plan Amendment 1
04DEC2018
Page 6
Abbreviation
Term
ECG
Electrocardiograms
ECOG
Eastern Cooperative Oncology Group
EDP
Exposure During Pregnancy
EDTA
Ethylenediaminetetraacetic Acid
EI
Equivalence Interval
ER
Estrogen Receptor
EudraCT
European Clinical Trials database
FDA
Food and Drug Administration
FFPE
Formalin-Fixed Paraffin-Embedded
FIP
First In Patient
FSH
Follicle Stimulating Hormone
GLP
Good Laboratory Practice
H&E
Hematoxylin and Eosin
HBV
Hepatitis B Virus
hCG
Human chorionic Gonadotropin
HCV
Hepatitis C Virus
HIV
Human immunodeficiency Virus
HNSTD
Highest Non-Severely Toxic Dose
ICH
International Conference on Harmonisation
ID
Identification
IEC
Institutional Ethics Committee
IHC
Immunohistochemistry
IND
Investigational New Drug
INR
International Normalized Ratio
IOP
Intraocular Pressure
IP
Investigational Product
IP
Intraperitoneal
IRB
Institutional Review Board
IUD
Intrauterine Device
IV
Intravenous
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Statistical Analysis Plan Amendment 1
04DEC2018
Page 7
Abbreviation
Term
LFT
Liver Function Tests
LSLV
Last Subject Last Visit
mAb
Monoclonal Antibody
MedDRA
Medical Dictionary for Regulatory Activities
mg/kg
Milligram/kilogram
MMAE
Monomethyl Auristatin E
MRI
Magnetic Resonance Imaging
MTD
Maximum Tolerated Dose
mTPI
Modified Toxicity Probability Interval
N/A
Not Applicable
NADPH
b-Nicotinamide Adenine Dinucleotide Phosphate
NCI
National Cancer Institute
NSCLC
Non-Small Cell Lung Cancer
ORR
Overall Response Rate
OVCA
Ovarian Cancer
PCD
Primary Completion Date
PD
Progressive Disease
PD
Pharmacodynamic
PDX
Patient Derived Xenograft
PE
Physical Exam
PFS
Progression Free Survival
P-gp
P-glycoprotein
PgR
Progesterone Receptor
PK
Pharmacokinetic
PR
Partial Response
PR
Pulse Rate
PS
Performance Scale
PT
Prothrombin Time
PTK7
Protein Tyrosine Kinase 7
Q3W
Once every 21 days
QTcF
Fridericia QT Correction Formula


Protocol B7661001 (PF-06647020)
Statistical Analysis Plan Amendment 1
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Page 8
Abbreviation
Term
rCyp
Human Recombinant Cytochrome P450
RECIST
Response Evaluation Criteria in Solid Tumors
RNA
Ribonucleic Acid
RP2D
Recommended Phase 2 Dose
RR
Response Rate
RTK
Receptor Tyrosine Kinase
SAE
Serious Adverse Event
SAP
Statistical Analysis Plan
SD
Stable Disease
SRSD
Single Reference Safety Document
STD10
Severely Toxic Dose for 10% of the animals
t½
Terminal Half-Life
TNBC
Triple Negative Breast Cancer
ULN
Upper Limit of Normal
UPCR
Urine Protein to Creatinine Ratio
UPM
Unit Probability Mass
US
United States
Vss
Volume of Distribution at Steady State
WBC
White Blood Cell
WFI
Water for Injection


Protocol B7661001 (PF-06647020)
Statistical Analysis Plan Amendment 1
04DEC2018
Page 9
1. AMENDMENTS FROM PREVIOUS VERSION(S) 
This amendment amends the original statistical analysis plan (SAP) in order to provide 
additional analysis and programming specifications for endpoints collected in the clinical 
Protocol Amendment 7, dated 15 May 2017. Note, there is a protocol amendment 8 dated 09 
November 2017 but it is for the United Kingdom only, it has no impact on this analysis plan.
2. INTRODUCTION
This document describes the planned statistical analyses for Protocol B7661001 Amendment 
7, dated 15 May 2017. This SAP is meant to supplement the study protocol.  This SAP 
supersedes the statistical considerations identified in the protocol and, where considerations 
are substantially different they will be identified as such. Any deviations from this analysis 
plan will be described in the clinical study report (CSR). Any post-hoc, or unplanned 
analyses performed that are not specified in this SAP will be clearly identified in the CSR.  
This plan is developed and finalized prior to database lock of the clinical database.  This SAP 
is written with consideration of the recommendations outlined in the International 
Conference on Harmonisation (ICH) E9 Guideline (Guidance for Industry: Statistical 
Principles for Clinical Trials) and on the ICH E3 Guideline (Guidance for Industry: Structure 
and Content of Clinical Study Reports).
2.1. Study Design
This is a Phase 1, open label, multi-center, non-randomized, multiple dose, safety,
pharmacokinetic and pharmacogenomic study, initially designed to evaluate single agent 
PF-06647020 in sequential cohorts of adult patients with advanced solid tumors unresponsive 
to currently available therapies or for whom no standard therapy is available.  Successive 
cohorts of patients received doses of PF-06647020 intravenously Q3W starting at a dose of
0.2 mg/kg.
This clinical study will include two parts.  Part 1 will estimate the MTD/RP2D in dose 
escalation cohorts in patients with advanced solid tumors unresponsive to currently available 
therapies or for whom no standard therapy is available.  Part 2 will explore benefit from 
treatment and to better define the safety profile, as well as the RP2D. 
 
 
 
 
This study also includes a DDI sub-study for evaluating the effect of multiple-dose 
fluconazole on the PK of unconjugated payload (PF-06380101).
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Statistical Analysis Plan Amendment 1
04DEC2018
Page 10
The DDI sub-study is an open-label, 2-period, fixed sequence design in up to 10 patients to 
determine the effect of multiple-dose fluconazole, a model moderate CYP3A4 inhibitor, on 
the PK of ADC (PF-06647020), total antibody (hu6M024 mAb) and unconjugated payload 
(PF-06380101), when fluconazole is co-administered with PF-06647020.  The sub-study will 
be in a separate cohort from the studies for TNBC, NSCLC and OVCA, and study design and
procedure details can be found in Appendix 7 of Protocol Amendment 7.
In Amendment 7, safety, PK and effectiveness of every 2 week (Q2W) dosing schedule for 
PF-06647020 as a single agent treatment or in combination with avelumab regimen will be 
evaluated in patients with platinum resistant or refractory OVCA and recurrent advanced 
NSCLC regimenwill be evaluated. 
Approximately, 190 patients are to be enrolled in this study (including Q2W Regimen 
Expansion).  The actual number of patients enrolled will depend upon tolerability of 
PF-06647020 and the number of dose levels required to identify the MTD/RP2D.
Patients will participate in the study for approximately 6 months or until disease progression, 
(PD) as per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) or irRECIST in 
Cohort 3 of the Q2W regimen expansion, patient withdrawal of consent or unacceptable
toxicity occurs, patient loss to follow up, or the study is terminated by the Sponsor, 
whichever comes first.  The projected 6 months study duration includes a 4 week screening 
period, a 4 month treatment period and a 4 week post dose follow-up period.  A follow-up 
visit within 4 weeks after the last dose of study drug for adverse event (AE) and serious 
adverse event (SAE) collection will be conducted.  The time on study can vary depending on 
the observed toxicity and potential benefit an individual patient derives.  The study is 
expected to be completed in approximately 36 months.
2.2. Study Objectives 
2.2.1. Dose Escalation (Part 1) Objectives
2.2.1.1. Primary Objectives

To assess safety and tolerability at increasing dose levels of PF-06647020
administrated intravenously on every 21-day dosing schedule to patients with
advanced solid tumors unresponsive to currently available therapies, or for whom no
standard therapy is available.

To determine the Maximum Tolerated Dose (MTD) and select the Recommended
Phase 2 Dose (RP2D).
2.2.1.2. Secondary Objectives

To evaluate the overall safety profile.

To characterize the single and multiple dose pharmacokinetics of ADC
(PF-06647020), total antibody (hu6M024 mAb) and unconjugated payload
(PF-06380101).


Protocol B7661001 (PF-06647020)
Statistical Analysis Plan Amendment 1
04DEC2018
Page 11
•
To evaluate the immunogenicity as measured by presence of anti-drug antibodies
(ADA) in patients treated with PF-06647020.
•
To document any preliminary evidence of anti-tumor activity.
•
.
2.2.2. Dose Expansion (Part 2) Objectives
2.2.2.1. Primary Objectives
•
To further evaluate safety and tolerability of PF-06647020 at the MTD and to 
establish RP2D in patients with NSCLC, TNBC and OVCA.
2.2.2.2. Secondary Objectives
•
To evaluate the overall safety profile at the RP2D.
•
To evaluate preliminary anti-tumor activity of PF-06647020 at the RP2D in patients 
with NSCLC, TNBC, and OVCA.
•
To evaluate the single and multiple dose PK of ADC (PF-06647020), total antibody 
(hu6M024 mAb), and unconjugated payload (PF-0638010).
•
To evaluate the immunogenicity as measured by presence of ADA in patients treated 
with PF-06647020.
•
To evaluate the effect of the co-administration of fluconazole on the PK of 
unconjugated payload (PF-06380101), ADC (PF-00647020) and total antibody 
(hu6M024 mAb) following administration of ADC (PF-06647020).
•
To assess the effects of fluconazole on the safety and tolerability of a single dose of 
PF-06647020. biomarkers in archival tumor biopsies, pre- and post-treatment tumor 
biopsies (if available).
•
 
 
•
 
 
•
 
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2.2.3. Objectives for Q2W Regimen
2.2.3.1. Primary Objectives
•
Part 1: To assess safety and tolerability at increasing dose levels of PF-06647020 
administered intravenously as a single agent on a Q2W dosing schedule.
•
Part 1: To determine the MTD and select the RP2D of PF-06647020 as a single agent 
treatment on a Q2W dosing schedule.
•
Part 2: To evaluate the overall safety profile of PF-06647020 as a single agent and in 
combination with avelumab at Q2W dosing schedule in OVCA and NSCLC patients 
at the RP2D.
[Ref: Appendix 8, Section A3 in Protocol Amendment 7].
2.2.3.2. Secondary Objectives
•
To characterize the single and multiple dose PK of ADC (PF-06647020), total 
antibody (hu6M024 mAb) and unconjugated payload (PF-06380101) when 
PF-06647020 administered alone or on combination with avelumab, and PK of 
avelumab. 
•
To evaluate the immunogenicity as measured by presence of ADA in patients treated 
with PF-06647020 or PF-06647020 in combination of avelumab. 
•
To evaluate anti-tumor activity of PF-06647020 as a single agent and when given in
combination with avelumab in patients with OVCA and NSCLC. 
[Ref: Appendix 8, Section A3 in Protocol Amendment 7].
2.2.3.3.
•
•
 
 
•
 
•
 
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Page 13
3. INTERIM ANALYSES, FINAL ANALYSES AND UNBLINDING 
This is an open-label, unblinded clinical trial.  Treatment safety and effectiveness are to be 
monitored continuously.  Upon all Part 1, Part 2 and DDI patients being treated for 72 weeks, 
if deemed necessary, an interim clinical study report may be generated to summarize safety, 
toxicity, PK/PD and clinical response of Q3W regimen..
4. HYPOTHESES AND DECISION RULES
4.1. Statistical Hypotheses
No formal hypothesis testing will be done.  .
4.2. Statistical Decision Rules
The initial Statistical Decision rulefor dose escalation based on a Bayesian mTPI procedure
are described in the following table:
Table 1.
Decision Rules
Number of patients treated at a Dose Level
DLT
n=2
n=3
n=4
n=5
n=6
n=7
n=8
n=9
n=10
n=11
n=12
0
E
E
E
E
E
E
E
E
E
E
E
1
na
S
S
S
E
E
E
E
E
E
E
2
U
D
D
S
S
S
S
S
S
S
S
3
U
U
D
D
S
S
S
S
S
S
4
U
U
U
D
D
D
D
D
S
5
U
U
U
U
U
D
D
D
6
U
U
U
U
U
U
D
7
U
U
U
U
U
U
D: De-escalate the dose; E: Escalate the dose; S: Stay at the dose; U:Unacceptable toxicity; na: Not applicable
5. ANALYSIS SETS
5.1. Full Analysis Set
The Full Analysis Set (FAS) is defined as all enrolled patients.
5.2. ‘PER PROTOCOL’ Analysis Set Evaluable for MTD
The per protocol analysis set includes all enrolled patients who receive at least one dose of 
study medication and who do not have major treatment deviations during first cycle with a 
baseline disease assessment and at least one post-baseline disease assessment.  Patients with 
major treatment deviations in the DLT observation period are not evaluable for the MTD 
assessment and will be replaced as needed to permit MTD estimation.  Major treatment 
deviations include:

Administration of less than 33% of the planned dose of PF-06647020 (provided that 
the reduction is not due to toxicity attributable to PF-06647020;


Protocol B7661001 (PF-06647020)
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•
Administration of more than 33% of the planned dose of PF-06647020 failure to
satisfy major entry criteria (eg, confirmation of the target disease, signed informed 
consent);
•
Use of other anticancer treatments during the active treatment and disease follow up 
phases other than as defined/allowed in this protocol;
•
A baseline disease assessment and at least one post-baseline disease assessment.
5.3. Safety Analysis Set
The Safety Analysis Set is defined as all patients who receive at least 1 full or partial dose of 
study medication.
5.4. OTHER ANALYSIS SETS
5.4.1. PK Concentration Analysis Set
The PK concentration analysis population is defined as patients who receive at least 1 dose of 
study treatment and who have at least 1 measurable concentration.
5.4.2. PK Parameter Analysis Set
The PK parameter analysis population is defined as patients who receive at least 1 dose of 
study treatment and have sufficient information to estimate at least 1 of the PK parameters of 
interest.
 
5.4.4. Immunogenicity Analysis Set
The immunogenicity analysis set is defined as patients who receive at least 1 dose of study 
treatment and have at least 1 ADA sample collected.
 
5.4.6. Drug-Drug Interaction (DDI) Study Analysis Set 
The DDI Study analysis set is defined as patients who participate in the drug-drug interaction 
substudy, and have at least one of the study required PK samples.
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5.5. Treatment Misallocations 
This is an unblinded MTD dose finding study.  Patients will be included in the cohort defined
by their initial dose.
5.6. Protocol Deviations
Protocol deviations will be defined and this analysis plan to be updated before database lock.
5.6.1. Deviations Assessed Orior to Randomization
At Screening, the investigator will assess subjects against the inclusion and exclusion criteria
as set out in Sections 4.1 and 4.2 of the protocol.
5.6.2. Deviations Assessed Post-Randomization
A full list of protocol deviations for the study report will be compiled prior to database 
closure.  Any significant deviation from the protocol will be reviewed prior to database 
closure and a decision taken regarding evaluation for each analysis population.
6. ENDPOINTS AND COVARIATES
Baseline is defined as the last planned visit measurement prior to the first dose of study 
medication administration; otherwise, the last available measurement prior to the first dose of 
study medication administration is to be adopted as Baseline. 
6.1. Efficacy Endpoints 
In this First in Patient study anti-tumor activity is a secondary objective.
Following assessments based on RECIST 1.1 are to be summarized:

Overall Response Rate (ORR).
The ORR is defined as the percentage of patients with best overall response (BOR) of CR or 
PR relative to the appropriate analysis set. 

Disease Control (DC).
A patient with a BOR of CR, PR, non-CR/non-PD or SD is defined as having DC. 
The DC rate is defined as the percentage of patients with DC according to the appropriate 
analysis set. In addition, a DC rate at week X would be to calculate a PFS Kaplan-Meier 
rate at week X.

Duration of Response (DoR).
For patients with an objective response, DoR is the time from first documentation of PR or 
CR to date of first documentation of PD or death due to any cause. 


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Censoring: Same as censoring for primary definition of progression free survival (PFS) used 
in the study.  Duration of response is only calculated on the subset of patients having CR or 
PR. 
•
Time to progression (TTP).
TTP is the time from start date to the date of the first documentation of PD.
•
Progression free survival (PFS).
PFS is the time from randomization date to date of first documentation of PD or death due to 
any cause.
Similar assessments based on irRECIST will be summarized.  The definitions for irBOR 
(including irCR, irPR, irSD, irPD etc.), irPFS, and irTTP are similar with those defined 
above based on RECIST 1.1 except that irRECIST criteria are used in defining each of the 
tumor response. 
6.2. Safety Endpoints
•
Dose Limiting Toxicity (DLT) is the primary endpoint of the dose escalation 
component of the study of both Q2W and Q3W regimen. 
•
Adverse Events (AEs): Treatment Emergent Adverse Events, those with initial onset 
or increasing in severity after the first dose of study medication.
•
AEs will be graded by the investigator according to CTCAE version 4.03 and coded 
using the Medical Dictionary for Regulatory Activities (MedDRA).  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.
•
Laboratory abnormalities.
•
Vital signs.
•
ECGs.
6.3.
 
•
 
 
 
•
 
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•
.
6.4. Pharmacokinetics Endpoints 
Drug concentrations of ADC (PF-06647020), total antibody (hu6M024 mAb), unconjugated 
payload (PF-06380101), and avelumab (combination of PTK7 ADC and avelumab cohort 
only) will be measured using validated methods.  PK parameters will be determined from the 
respective concentration-time data using standard noncompartmental methods.  Actual 
sample collection times will be used for the parameter calculations.  For ADC 
(PF-06647020), total antibody (hu6M024 mAb), and avelumab (PTK7 ADC in combination 
of avelumab cohort) , PK parameters including maximum concentration (Cmax), time to 
maximum concentration (Tmax), area under the concentration-time curve over 1 dosing 
interval (AUCτ), area under the concentration-time curve from time 0 to the last measurable 
concentration (AUClast), and if data permit or if considered appropriate, area under the 
concentration-time curve from time 0 extrapolated to infinity time (AUCinf), terminal 
elimination half-life (t½), clearance (CL), volume of distribution at steady state (Vss), and 
accumulation ratio (Rac) will be calculated.  For unconjugated payload (PF-06380101), PK 
parameters including Cmax, Tmax, AUClast, AUCinf, AUCτ, t½,  and Rac will be calculated 
as appropriate.  For avelumab, PK parameters including Cmax, Tmax, AUClast, AUCinf, 
AUCτ, t½, CL, Vss and Rac will be calculated as appropriate.
PK parameters will be derived from the concentration-time data as follows:
Parameter
Definition
Method of Determination
AUClast
Area under the concentration-time 
profile from time zero to the time of 
the last quantifiable concentration
Linear/Log trapezoidal method
AUCτ
Area under the concentration-time 
profile from time zero to the time τ, 
the dosing interval
Linear/Log trapezoidal method
AUCinf
Area under the concentration-time 
profile from time zero extrapolated to 
infinite time
AUC(0-t[last]) + (Clast*/kel),
where Clast* is the predicted serum concentration at 
the last quantifiable time point estimated from the 
log-linear regression analysis.
Cmax
Maximum observed concentration
Observed directly from data
Tmax
Time for Cmax
Observed directly from data as time of first 
occurrence
T½
Terminal elimination half-life
Loge(2)/kel,
where kel is the terminal phase rate constant 
calculated by a linear regression of the log-linear 
concentration-time curve.  Only those data points 
judged to describe the terminal log-linear decline will 
be used in the regression.
CL
Clearance
Dose/ AUCinf for cycle 1; Dose/ AUCτ for cycle 4
Vss
Volume of distribution at steady state
CL×MRT
Rac
Observed accumulation ratio
AUC cycle 4, τ/ AUCcycle 1, τ
Blood samples collected for fluconazole concentrations (DDI study only) will only be 
analyzed if fluconazole concentration data are required for interpreting the PF-06380101 PK 
results.
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6.5. PD Endpoint
  Samples will be assayed using a validated analytical 
method in compliance with Pfizer standard operating procedures.
 
 
 
 
6.6. Immunogenicity Endpoints
For the immunogenicity data, the percentage of patients with positive ADA of PF-06647020 
or avelumab, and Nab each will be summarized by dose level (Part 1) or by treatment arms 
(Part 2).  For patients with positive ADA or Nab, the magnitude (titer), time of onset, and 
duration of ADA or Nab response will also be described, if data permit.  Potential impact of 
immunogenicity on PK and 
, safety/tolerability and 
efficacy of PF-06647020 will be explored, if data is warranted. 
6.6.1. Outcomes Research Endpoints
Not applicable
6.7. Covariates 
The analyses of the MTD do not use covariates, and none will be defined.  There are no 
planned comparisons between dose groups. 
7. HANDLING OF MISSING VALUES
Missing data will be excluded from the tabular summaries.
8. STATISTICAL METHODOLOGY AND STATISTICAL ANALYSES
8.1. Statistical Methods
The statistical summaries are non-inferential.  The data are summarized by cohort defined by 
the initial dose of the study drug.  Where applicable the summaries of the MTD may include 
a Bayesian credible interval based on the posterior density from the full probability model.
8.1.1. Analyses for Continuous Data
Continuous data will be summarized with the mean, median, minimum, maximum and 
standard deviation.  Missing values will be excluded from the analysis.
8.1.2. Analyses for Categorical Data 
Categorical data will be summarized by number of unique patient incidence.  Missing data 
will be excluded from the analysis.
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8.1.3. Analyses for Binary endpoints
Binary data will be summarized using number of unique patient incidence, and Wilson’s 
confidence interval for binomial proportions may be presented.
8.1.4. Analyses for Time-to-Event Data
The median, percentiles and probabilities at particular points in time are estimated using the 
method of Kaplan and Meier. 
8.2. Statistical Analyses 
8.2.1. Primary Analysis
The primary analysis will be based on the Safety Analysis Set.  The analysis is to summarize 
the adverse event incidence and will implement Pfizer standard summaries for adverse 
events.  The occurrence of DLTs observed in the dosing cohorts is used to estimate the MTD 
as described in the Study Design section.  Adverse Events constituting DLTs will be listed 
per dose level.  Because the intent is to find a desirable dose that meets the tolerability 
criteria based on DLT rate while demonstrating clinical activity based on response rate, 
descriptive statistics (n, frequency, and percentage) will be resorted.  Corresponding listings 
of data will be generated.
8.2.2. Efficacy Analyses
No formal hypothesis testing will be performed on analysis of efficacy endpoints.  Efficacy 
analysis will be summarized by dosing regimen, tumor type and dose.
Descriptive statistics (frequency and percentage) for tumor response (CR, PR, PD, SD, etc.), 
ORR, DCR will be presented, based on RECIST 1.1 and irRECIST, separately. 
The time to event endpoints such as PFS, TTP, and DOR will be summarized using the 
Kaplan Meier method.  DOR is only for the subset patients who achieved the best overall 
response (BOR, or irBOR) of CR (irCR) or PR (irPR), and may also be summarized as a 
general continuous variable for which mean, standard deviation, minimum, maximum and 
median of duration in unit of weeks.
8.2.2.1. Progression-Free Survival (PFS)
PFS is the time from randomization date to date of first documentation of PD or death due to 
any cause. 
PD or death within 16 weeks of the last adequate tumor assessment or start date will be 
counted as an event according to the tumor assessment date or date of death, as appropriate. 
Censoring: Patients without an event or with an event more than 16 weeks after the last 
adequate tumor assessment will be censored on the date of the last adequate tumor
assessment that documented no progression.  In addition, if a new anti-cancer therapy is 
started prior to an event; the patient will be censored on the date of the last adequate tumor 
assessment that documented no progression prior to the start of the new anti-cancer therapy.


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An adequate post-baseline assessment is defined as an assessment where a response of CR, 
PR, SD, non-CR/non-PD, or PD can be determined based on RECIST 1.1 and/or irRECIST 
(for combination cohort only) criteria.  Time points where the response is NE or no 
assessment was performed will not be used for determining the censoring date. 
Patients with no baseline tumor assessment (including patients with an inadequate baseline 
assessment) or with no adequate post-baseline tumor assessments within 16 weeks after the 
start date will be censored on the start date, unless the patient dies within 16 weeks of the 
start date,  in which case, death will be an event on date of death. 
Events and censoring rules are summarized in Table 2.
Table 2.
PFS Outcome and Event Dates
Situation
Date of 
Progression/Censoring
Outcome
No adequate baseline assessment
Start datea
Censoreda
PD or death 16 weeks after last 
adequate tumor assessment or 
16 weeks after start date
Date of PD or death
Event
No PD/withdraw due to clinical
progression
Date of last adequate tumor 
assessment 
Event
PD or death >16 weeks after the last 
adequate tumor assessmentb 
Date of last adequate tumor 
assessmentb documenting no 
PD prior to new anti-cancer 
therapy or missed 
assessments
Censored
No PD
New anti-cancer therapy given 
a If the patient dies ≤16 weeks after start date, the death is an event with date on death date.
b If there are no adequate post-baseline assessments prior to the PD or death, then the time without adequate 
assessment should be measured from the start date; if the criteria were met the censoring will be on the start 
date.
Reasons for censoring should be summarized according to the categories in Table 3.


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Table 3.
PFS Censoring Reasons and Hierarchy
Hierarchy
Condition
Censoring Reason
1
No adequate baseline assessment.
No adequate baseline 
assessment
2
Start of new anti-cancer therapy before event. 
Start of new anti-cancer 
therapy
3 
Event more than 16 weeks from last adequate 
post-baseline tumor assessment/start date.
Event after missing 
assessmentsa
4
No event and [withdrawal of consent date ≥start 
date OR End of study (EOS) = Subject refused 
further FU].
Withdrawal of consent
5
No event and lost to follow-up in any 
disposition page.
Lost to follow-up
6
No event and [EOS present OR disposition page 
for any EPOCH after screening says patient will 
not continue into any subsequent phase of the 
study] and no adequate post-baseline tumor 
assessment.
No adequate post-baseline 
tumor assessment
7 
No event and none of the conditions in the prior 
hierarchy are met.
Ongoing without an event
a More than 16 weeks after last adequate tumor assessment. 
8.2.2.2. Time to progression (TTP)
TTP is the time from start date to the date of the first documentation of PD. 
In TTP analysis, deaths are censored, either at the time of death or at an earlier visit 
representing informative censoring (non-random pattern of loss from the study). 
Censoring:  Same as censoring for the definition of PFS.  In addition patients who die 
without PD will be censored on the date of the last adequate tumor assessment that 
documented no progression.
Events and censoring rules are summarized in Table 4 similarly to PFS but not including 
death as an event.


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Table 4.
TTP Outcome and Event Dates
Situation
Date of Progression/Censoring
Outcome
No adequate baseline assessment
Start date
Censored
PD 16 weeks after last adequate tumor 
assessment or 16 weeks after start date
Date of PD
Event
No PD/ withdraw due to clinical progression
Date of last adequate tumor 
assessment 
Event
Date of last adequate tumor 
assessmenta documenting no PD 
prior to new anti-cancer therapy or 
missed visits.
Censored
No PD
New anti-cancer therapy given 
Death due to any cause
Reasons for censoring should be summarized according to the categories in Table 5.
Table 5.
TTP Censoring Reasons and Hierarchy
Hierarchy
Condition
Censoring Reason
1
No adequate baseline assessment
No adequate baseline 
assessment
2
Start of new anti-cancer therapy before PD.
Start of new anti-cancer 
therapy
3 
Event more than 16 weeks from last 
adequate post-baseline tumor 
assessment/start date
Event after missing 
assessmentsa
4
Death prior to PD
Death due to any cause
4
No PD and [withdrawal of consent date ≥
start date OR End of study (EOS) = Subject 
refused further FU]
Withdrawal of consent
5
No PD and lost to follow-up in any 
disposition page 
Lost to follow-up
6
No PD and EOS present OR disposition 
page for any EPOCH after screening says 
patient will not continue into any 
subsequent phase of the study] and no 
adequate post-baseline tumor assessment
No post-baseline tumor 
assessment
7 
No PD and none of the conditions in the 
prior hierarchy are met
Ongoing without an event
A more than 16 weeks after last adequate tumor assessment. 


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8.2.2.3. Duration of Response (DoR)
For patients with an objective response, DoR is the time from first documentation of PR or 
CR to date of first documentation of PD or death due to any cause. 
Censoring: Same as censoring for primary definition of PFS used in the study.
8.2.2.4. Overall Response Rate (ORR)
The ORR is defined as the percentage of patients with a BOR of CR or PR relative to the 
appropriate analysis set.
Category of Best Overall Response:
Best overall response: The BOR is the best response recorded from start date until the end of 
study, disease progression or start of new anti-cancer therapy whichever is earlier. 
CR: Two objective statuses of CR a minimum of four weeks apart documented before 
progression and start of new anti-cancer therapy.
PR: Two objective statuses of PR or better (PR followed by PR or PR followed by CR) a 
minimum of four weeks apart documented before progression and start of new anti-cancer 
therapy, but not qualifying as CR.  Sequences of PR- Stable- PR are considered PRs as long 
as the two PR responses are observed at a minimum of 4 weeks apart.
SD: At least one objective status of stable or better documented at least 6 (-.5) weeks (in 
consideration of study monitoring schedule) after start date and before progression and the 
start of new anti-cancer therapy but not qualifying as CR or PR. 
PD: Progression documented after start date and not qualifying as CR, PR , SD or NE. 
Not Evaluable (NE): All other cases.  Note that reasons for NE should be summarized and 
the following reasons could be used:

Early death : death prior to 6 weeks after start date;

No post-baseline assessments;

All post-baseline assessments have overall response NE;

New anti-cancer therapy started before first post-baseline assessment;

SD too early (<6 (-0.5) weeks after start date).
Special and rare cases where BOR is NE due to early SD will be classified as ‘SD too early’.


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An objective status of PR or SD cannot follow one of CR.  SD can follow PR only in the rare 
case that tumor increases by less than 20% from the nadir, but enough that a previously 
documented 30% decrease from baseline no longer holds.  If this occurs, the sequence 
PR-SD-PR is considered a confirmed PR.  A sequence of PR – SD – SD – PD would be a 
best response of SD if the window for SD definition has been met.
Derivation of BOR and irBOR
Examples of objective status sequences and overall response for a tumor assessment interval 
of at least 4 weeks and at least as long as the minimum assessment time to qualify as SD are 
shown in Table 3.  This will vary for other assessment schedules. 
Table 6.
Derivation of Best Overall Response When Confirmation Of Response Is 
Required
Objective status at:
Assessment 1
Assessment 2
Assessment 3
Assessment 4
Overall Response
Death 
NE
CR
CR
PD 
CR
CR
NE
CR
PD
CR
PR
CR
CR
PD
CR
PR
CR
PD 
PR
PR
PR
PD
PR
PR
SD or NE
PR
PD
PR
PR
PR
CR
PD
PR
CR
PR
Not allowed.  
Reappearance is 
progression  
CR
PD
SD 
PR
PD
SD 
SD or NE
CR
PD
SD 
SD or NE
PR
PD
SD 
SD
PD 
SD
PD 
PD
No or NE assessment 
NE
NE
PD
PD
NE
No or NE assessment
NE
NE
NE
PD 
NE 


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Table 7.
Scenarios of Assignments of Best Overall Response using irRECIST
Objective status at:
Assessment 1
Assessment 2
Assessment 3
Assessment 4
ir Best Overall Response
Death 
NE
irCR
irCR
irPD 
irCR
irCR
NE
irCR
irPD
irCR
irPR
irCR
irCR
irPD
irCR
irPR
irCR
irPD 
irPR
irPR
irPR
irPD
irPR
irPR
irSD or NE
irPR
irPD
irPRa
irPR
irPD
irPR
irSD
irPR
irPR
irCR
irPD
irPR
irCR
irPR
irPR
irCR
irPD
irSD 
irPR
irPD
irSD 
irPR
irSD
irSD or NE
irCR
irPD
irSD 
irSD or NE
irPR
irPD
irSD 
irSD
irPD 
irSD
irPD
irPD
irPD
irPD
Death
irPDb
irPD 
NE
No or NE 
assessment 
NE
NE
irPD
NE
NE
No or NE 
assessment
NE
NE
NE
irPD 
NE 
a. if irPRs are at least 4 weeks apart; b.  Death due to disease progression
“ir” indicates immune responses assigned using irRECIST. irBOR=best overall response. irCR=complete 
response. irPR=partial response. NE=not evaluable. irPD=confirmed progression. irSD=stable disease.  
RECIST=Response Evaluation Criteria in Solid Tumors.
8.2.2.5. Disease Control Rate (DCR)
A patient with a BOR of CR, PR, non-CR/non-PD or SD is defined as having Disease 
Control.
The DCR is defined as the percentage of patients with DC according to the appropriate 
analysis set. 
8.2.2.6. Clinical Benefit Response (CBR)
The clinical benefit response is defined as a CR, PR or SD lasting for 6 cycles or greater.  
CBR rate with 95% confidence interval will be tabulated by dosing regimen and tumor type.
8.2.3. Safety Analyses
Safety data will be summarized using Pfizer standard data summary procedures. 
Data will be summarized by dosing regimen and dose. 


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A breakdown of demographic data will be provided for age, race, weight, body mass index, 
and height by cohort defined by initial dose. 
Adverse Events, 
AEs including irAE (combination cohort only) will be graded by the investigator according 
to the CTCAE version 4.03 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 CTCAE grade definitions, results will be categorized as normal, 
abnormal high/low or not done.
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 line of therapy, medical history, Eastern 
Cooperative Oncology Group (ECOG) performance status, baseline CA-125 and primary 
diagnosis will be tabulated and listed by dose and dosing regimen, and by tumor type and 
dosing regimen.  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 for the Q3W 
Regimen and 28 days for the Q2W Regimen.  Day 1 of a cycle is the date of first dose within 
that cycle.  The safety analysis set will be used.


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Dose modifications may occur in the following ways:

Cycle delay—Day 1 of current cycle starts later than 28 days from Day 1 of the 
previous cycle (only applies to cycle 2 and above) for the Q3W Regimen.  Day 1 of 
current cycle starts later than 35 days from Day 1 of the previous cycle for the Q2W 
Regimen; 

Dose reduction—A decrease greater than 0.5 mg/kg equivalent in the administered 
total daily dose 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;

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).


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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 0 mg), 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.  Summary tables, listings of prior, 
concomitant, and further therapies will be provided separately.
Anti-PF-06647020 and anti-avelumab antibody
For anti- PF-06647020 and anti-avelumab antibody, a listing, sorted by subject and study 
day, of the result of specific ADAantibody at screening (positive/negative [<1:negative]), the 
specificity, and titer will be listed.  Summary counts of the patients, who are positive for the 
antibody, will be derived by study treatment and visit for the safety population.  No summary 
statistics other than those cited above, will be generated.
The following data will also be summarized by treatment and in accordance with the current 
sponsor reporting standards:
Discontinuations, Adverse Events, laboratory data, vital signs, ECG and concomitant 
medication data will be summarized by cohort defined by initial dose in accordance
with current Pfizer data standards.
It should be recognized that most studies are not designed to reliably demonstrate a causal 
relationship between the use of a pharmaceutical product and an adverse event or a group of 
adverse events.  Except for select events in unique situations, studies do not employ formal 
adjudication procedures for the purpose of event classification.  As such, safety analysis is 
generally considered as an exploratory analysis and its purpose is to generate hypotheses for 
further investigation. 
8.2.4. Other Safety Data – Screening and Other Special Purpose Data
Prior medication(s), non-drug treatment(s), medical history and physical examination will be 
listed in accordance with the sponsor reporting standards.  Medical history will be mapped 
using the MedDRA thesaurus.


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Serum/urine Pregnancy test results will be presented in the listings.
8.2.5. PK Analyses
8.2.5.1. 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.)
8.2.5.2. Deviations, Missing Concentrations and Anomalous Values
In summary tables and plots of the median values at each time point, statistics will be 
calculated having set concentrations to missing if 1 of the following cases is true:
1. A concentration has been collected as ND (ie not done) or NS (ie no sample),
2. A deviation in sampling time is of sufficient concern or a concentration has been 
flagged anomalous by the pharmacokineticist.
Note that summary statistics will not be presented at a particular time point if more than 50% 
of the data are missing.
8.2.5.3. Pharmacokinetic Parameters 
Actual PK sampling times will be used in the derivation of PK parameters.  Each PK 
parameter will be summarized by regimen, dose and cycle and will include the set of 
summary statistics as specified in the table below: 
Parameter
Summary statistics
AUClast, AUC∞, 
AUC, Cmax, CL, 
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
To assess the relationship between the PK parameters and dose, dose normalized AUC∞, 
AUClast, AUC, and Cmax will be plotted against regimen, dose (using a logarithmic scale), 
and will include individual subject values and the geometric means for each dose.  Geometric 
means will have a different symbol than the individual values.  The values will be dose 
normalized (to a 1 mg/kg dose) by dividing the individual values and raw geometric means 
by dose.  A footnote will be added to the plots to indicate that geometric means are presented 
are presented on the plot.  


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8.2.5.4. PK Concentrations
To assess the PK profiles of PF-06647020 (ADC), total antibody, unconjugated payload, and 
avelumab (PTK7 ADC in combination of avelumab cohort), PK concentrations of each 
analyte will be listed, summarized and plotted for subjects in the PK analysis set (as defined 
in Section 5.4), where missing and BLQ values will be handled as detailed in Section 8.2.5.1
above.
Presentations for each PK analyte will include:

A listing of all concentrations sorted by dose, subject ID, period and nominal time 
post-dose.  The listing of concentrations will include the actual sample collection 
times, and the time of dosing.  Deviations from the nominal time will be given in a 
separate listing.

A summary of concentrations by dose and nominal time post-dose, where the set of 
statistics will include n, mean, median, standard deviation, coefficient of variation 
(cv), minimum, maximum and the number of concentrations above the lower limit of 
quantification.

Median concentrations against nominal time post-dose by dose (based on the 
summary of concentrations by dose and time post-dose), with all doses presented on 
the same plot.  Two plots will be generated, so that the concentrations can be 
presented on linear and logarithmic scales.

Mean concentrations against nominal time post-dose by dose (based on the summary 
of concentrations by dose and time post-dose), with all doses presented on the same 
plot.  Two plots will be generated, so that the concentrations can be presented on 
linear and logarithmic scales.

Plots of individual concentrations against actual time post-dose (separate plots for 
each dose).  Two plots per dose will be generated, so that the concentrations can be 
presented on linear and logarithmic scales.

Plots of concentration against actual time post-dose by subject (separate line for each 
dose).  Two plots per subject will be generated, so that the concentrations can be 
presented on linear and logarithmic scales.
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 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.


Protocol B7661001 (PF-06647020)
Statistical Analysis Plan Amendment 1
04DEC2018
Page 31
8.2.6. Drug-Drug Interaction Analysis (DDI sub-study only) 
For DDI sub-study, the primary PK parameters for puopose of evaluating drug interactions 
will be dose normalized AUC∞, AUClast, AUC, and Cmax for unconjugated payload 
(PF-06380101) in the absence (Reference) and presence (Test) of fluconazole.  AUC 
parameters and Cmax will be natural log transformed and subjected to ANOVA test; the 
adjusted mean differences (Reference – Test) and corresponding 90% confidence intervals 
(CIs) will be derived.  The adjusted mean differences and 90% CIs for the differences will be 
exponentiated to provide estimates of the geometric mean ratios (GMRs) and the associated 
90% CIs.  No formal confirmatory hypothesis testing will be conducted.
A similar analysis will be conducted for ADC (PF-06647020), total antibody (hu6M024 
mAb), and unconjugated payload/ADC exposure ratios (AUC, Cmax), as supportive data. 
Summary statistics and figures of Cmax and AUC values of unconjugated payload 
(PF-06380101), ADC (PF-06647020), total antibody (hu6M024 mAb), as well as 
unconjugated payload/ADC exposure ratios will be presented by Cycles (Cycle 1 - ADC 
alone vs. Cycle 2 - ADC in the presence of fluconazole).  Data from patients prematurely 
ending participation in the study or failing to meet evaluation criteria may be excluded from 
pharmacokinetic data evaluation.
Presentations for each PK analyte will include:

Median concentrations against nominal time postdose following administration of 
PF-06640707 without and with fluconazole (cycle 1 vs. cycle 2).  Two plots will be 
generated, so that the concentrations can be presented on linear and logarithmic 
scales.

Dose normalized median concentrations against nominal time postdose following 
administration of PF-06640707 without and with fluconazole (cycle 1 vs. cycle 2).  
Two plots will be generated, so that the concentrations can be presented on linear and 
logarithmic scales.

Mean concentrations against nominal time postdose following administration of 
PF-06640707 without and with fluconazole (cycle 1 vs. cycle 2).  Two plots will be 
generated, so that the concentrations can be presented on linear and logarithmic 
scales.

Dose normalized mean concentrations against nominal time postdose following 
administration of PF-06640707 without and with fluconazole (cycle 1 vs. cycle 2).  
Two plots will be generated, so that the concentrations can be presented on linear and 
logarithmic scales.

Plots of individual concentrations against actual time postdose following 
administration of PF-06640707 without and with fluconazole (cycle 1 vs. cycle 2).  


Protocol B7661001 (PF-06647020)
Statistical Analysis Plan Amendment 1
04DEC2018
Page 32
Two plots will be generated, so that the concentrations can be presented on linear and 
logarithmic scales.
 
 
 
 
CCI


Protocol B7661001 (PF-06647020)
Statistical Analysis Plan Amendment 1
04DEC2018
Page 33
9. REFERENCES 
1.
Y. Ji, Y. Li And G. Yin Bayesian Dose Finding In Phase I Clinical Trials Based On A 
New Statistical Framework, Statistica Sinica 17(2007), 531-547 E.A. Eisenhauer, P. 
Therasse, J. Bogaerts, et al. New response evaluation criteria in solid tumors: Revised 
RECIST guideline (version 1.1). Euro J. Cancer 2009; 92: 205-216. 
2.
L. Seymour, J. Bogaerts, A. Perrone, et al, iRECIST: guidelines for response criteria for 
use in trials testing immunotherapeutics. Lancet Oncology, 2017; 18: e143-52.
3.
Food and Drug Administration Guidance For Industry Clinical Trial Endpoints For The 
Approval Of Cancer Drugs And Biologics 
http://www.fda.gov/downloads/Drugs/.../Guidances/ucm071590.pdf.