PHASE 1/2 STUDY OF PF-06463922 (AN ALK/ROS1 TYROSINE KINASE INHIBITOR) IN PATIENTS WITH ADVANCED NON-SMALL CELL LUNG CANCER HARBORING SPECIFIC MOLECULAR ALTERATIONS
Phase: PHASE1
Conditions: ALK-positive Non Small Cell Lung Cancer (NSCLC) and ROS1-positive NSCLC
Sponsor: Pfizer

PF-06463922 
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Final Protocol Amendment 8, 23 January 2019 
PFIZER CONFIDENTIAL 
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PHASE 1/2 STUDY OF PF-06463922 (AN ALK/ROS1 TYROSINE KINASE 
INHIBITOR) IN PATIENTS WITH ADVANCED NON-SMALL CELL LUNG 
CANCER HARBORING SPECIFIC MOLECULAR ALTERATIONS 
 
Compound: 
PF-06463922 
Compound Name: 
Not Applicable (N/A) 
United States (US) Investigational New 
Drug (IND) Number: 
European Clinical Trial Database 
(EudraCT) Number: 
118,296 
 
2013-002620-17 
 
Protocol Number: 
B7461001 
Phase: 
1/2 
 
 
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by accepting or reviewing this document, you agree to hold this information in confidence and not copy or 
disclose it to others (except where required by applicable law) or use it for unauthorized purposes. In the event 
of any actual or suspected breach of this obligation, Pfizer must be promptly notified. 

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Document History 
 
Document 
Version Date 
Summary of Changes and Rationale 
Amendment 8 
23 January 2019 
Since the primary endpoint of the study has 
been met and secondary endpoints 
characterized, the main purpose of the 
amendment is to fulfill the obligation to 
provide drug supply and standard of care to 
the patients still receiving a benefit from the 
study drug. Therefore, a reduced Schedule of 
Assessments is introduced allowing to 
perform most study procedures per standard 
of care or clinical judgment of treating 
physician. Data recording will be limited to 
adverse events, with the purpose of 
performing long term safety assessments and 
overall survival. Further clarification on dose 
modifications section (5.2.7) and management 
of toxicities guidelines. 
Update to Section 5.2, PF-06463922 will not 
be supplied anymore as 5 mg tablets. 
Revision to Concomitant Treatments section 
5.3 to align with the PF-06463922 approved 
label. 
Hormonal contraceptives not listed anymore 
as a highly effective method because they are 
metabolized by CYP3A, which may be 
induced by PF-06463922. Pregnancy test 
assessments frequency increased by adding 
every cycle monitoring during the study 
treatment, and at first follow-up visit. 
Contraceptive check frequency increased by 
adding every cycle monitoring during the 
study treatment and subsequent follow-up. 
Changes to Analysis Set definitions, to match 
SAP V5.0 finalized after Protocol 
Amendment 6 removing the Evaluable for 
Response Analysis Sets and to incorporate 
regulatory recommendation on ITT definition. 
Added clarifications on pooled/subgroup 

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analyses. 
Added clarifications on the evaluation of 
Disease Control Rate at 12 and 24 weeks. 
Added details on analysis of DDI cohort. 
End of trial definition updated. 
Amendment 7 
23 March 2018 
Clarification to Section 1.3.5, Section 4.1, and 
Section 4.3.1 regarding the requirement for all 
sexually active men to use a condom through 
97 days after the last dose of PF-06463922 to 
prevent any transfer and exposure of study 
drug to the partner given the known 
embroyonic and fetal toxicity risk. 
Additonal monitoring (Transthoractic 
Echocardiogram) for patients enrolled in 
France and Germany per the request of Health 
Authorities in those countries. 
Table 5, Footnote 16, updated to remove 
9 hour PK timepoint as this is a typo. Also 
removed from Section 7.2.8. 
Added Appendix 13, which is required for 
sites in France only. 
Amendment 6 
15 July 2016 
Addition of Drug-Drug interaction (DDI) and 
Holter Monitoring in parallel with the 
ongoing Phase 2 part of the study. Added 
language in applicable sections to include this 
study. 
Study Endpoints, Study Objectives, and the 
Statistical Analysis section updated to support 
the DDI and Holter monitoring and the 
Statistical Analysis Plan. 
Addition of exclusion criteria and clarification 
of inclusion criteria for patients participating 
in the DDI and Holter monitoring in Phase 2. 
Clarification to Exclusion Criteria 4; patients 

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who experience clinically significant tumor 
flare may begin treatment with a shortened 
prior systemic washout period, after 
discussion with the sponsor. 
Removal of some required assessments in 
Phase 1, Phase 2, and Japanese Patient Only 
Lead-In Cohort (LIC), and reduction of 
frequency in some assessments in Phase 1, 
Phase 2, and Japanese LIC. 
Allowance of Fine Needle Aspiration (FNA) 
samples as a substitute for De Novo biopsies 
in both Phase 1 and Phase 2 only if De Novo 
biopsy is not safe or feasible. 
Adjustment in the sample sizes of 
ALK-positive patient subgroups being studied 
in Phase 2. Updated Statistical Analysis 
Section to correlate with this change. 
Increase in overall sample size in Phase 2 and 
overall sample size in the study. 
Revised Dose Modification Guideline for 
patients who experience first-degree, 
second-degree or complete heart block. 
Removed food and beverage restriction as it 
relates to PF-06463922 dosing requirements. 
Removal of restriction for taking proton pump 
inhibitors (PPI) concomitantly with 
PF-06463922. 
Minor other clarifications throughout. 
Amendment 5 
11 March 2016 
Updated the Background sections to include 
new data in animals relating to the association 
of lorlatinib and teratogenicity. Minor related 
changes made to the Contraception section 
without changes made to contraception 
guidance. 
Updated the Background sections to include 

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new information on PR interval prolongation 
as seen in a healthy volunteer study and in 
Study B7461001. 
Updated Exclusion Criterion 9 to exclude 
patients with a PR interval >220 msec, or 
2nd- or 3rd-degree AV block within 3 months 
prior to study entry and to align with other 
ongoing and planned Pfizer-sponsored 
clinical trials with PF-06463922. 
Added a dose modification guideline for 
patients with PR interval prolongation in 
Section 5.2.7. 
Added Appendix 12 which provides examples 
of drugs known to prolong PR interval. 
Minor administrative edits made to the 
Adverse Event and Reporting and Publication 
of Study Results sections. 
Amendment 4 
22 July 2015 
Identification and justification of 
Recommended Phase 2 Dose (RP2D), 
including available safety, pharmacokinetics, 
and efficacy data from Phase 1. 
Alignment of Phase 1 and Phase 2 Study 
Objectives and Endpoints. 
Update to the type and allocation of patients 
in the subgroup categories (EXP) in Phase 2. 
Increase in Phase 2 sample size. 
Revisions of Patient Inclusion Criteria; 
clarification of patient population entry 
criteria relating to prior treatment, 
modification of serum total amylase 
requirement and removal of alkaline 
phosphatase requirement. Additionally, 
removal of requirement for negative 
pregnancy test at baseline visit. 
Revision of Patient Exclusion Criteria; 

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removal of patients who are in the locally 
advanced disease setting, exclusion of 
patients who have had prior treatment with 
antibody therapy or drugs specifically 
targeting T-cell co-stimulation or immune 
checkpoint pathways, removal of exclusion 
criteria relating to contraindication to 
midazolam (MDZ) administration as this 
substudy is no longer required in Phase 2, 
exclusion of patients requiring drugs that are 
strong CYP2C19 and/or CYP2C8 inhibitors, 
exclusion of patients requiring drugs that are 
known P-gp substrates with a narrow 
therapeutic index, and exclusion of pregnant 
women or breastfeeding women per country 
requirement. Additional clarification that 
patients with bradycardia are not excluded if 
otherwise healthy (eg, runners, etc.). 
Addition of optional crizotinib treatment after 
PF-06463922 in Phase 2 for ALK+ NSCLC 
patients who were treatment naïve prior to 
receiving PF-06463922. Added Safety 
Reference Documents for crizotinib. 
Removal of some required assessments in 
Phase 2 including Midazolam substudy, Food 
Effect substudy, some PK requirements, 
Urine Sample for 6 beta-Hydroxycortisol/ 
Cortisol (6-OHC/C) Ratio, Blood for 
beta-Hydroxycholesterol/Cholesterol, Mini 
Mental State Examination, and Blood 
Specimen for Circulating Tumor Cell (CTC) 
enrichment. 
Revisions to the PK requirements, including 
timepoints, in Phase 2. 
Addition of some required assessments in 
Phase 2 including assessments of Cognition, 
Mood and Suicidal Ideation and Behavior 
(SIB) and Contraceptive check (as 
appropriate). Added the requirement for a 
rater at each site to administer the assessments 
of Mood and Suicidal Ideation and Behavior 

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(SIB). 
Change in sample size of patients receiving 
Lead-In Dose in Phase 2 from 30 patients to 
approximately 10 Non-Japanese patients and 
3 Japanese patients. 
Revision to the timepoint requirements in 
Phase 2 for Electrocardiogram (ECG) 
collection and PK collection. 
Clarification that some of the required 
laboratory assessments in Phase 2 (chemistry, 
hematology, coagulation, lipids, and 
urinalysis) may be performed within 72 hours 
of the next cycle start. 
Clarification that Cerebrospinal Fluid (CSF) 
in Phase 2 will only be collected at Screening 
for those patients who have suspected or 
confirmed Leptomeningeal Carcinomatosis 
not visualised on MRI. After Screening, CSF 
collection is not required. 
Clarification that for patients in Phase 2 who 
have not had prior systemic therapy in the 
locally advanced or metastatic disease setting, 
a de novo biopsy sample is not required 
unless the previous sample was collected 
>4 months after the first PF-06463922 dose. 
Additional clarification that tumor tissue 
slides are acceptable if country regulations 
prevent sending core biopsy sample. 
Revision of Dose Modification Tables for 
Phase 1 and Phase 2 including the addition of 
specific Dose Modifications for 
Non-Hematologic toxicities, Hematologic 
toxicities, Lipid Elevations, and Central 
Nervous System (CNS) effects. Added a 
Dose Reduction Table for Phase 2. 
Added requirement for submission of 
radiographic images to a Central Core 

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Imaging Laboratory in Phase 
1 (retrospectively) and Phase 
2 (prospectively). 
Updated PF-06463922 drug packaging and 
tablet strength information in Phase 2. 
Revision to Concomitant Treatment and 
Medication Section; added data available 
from Phase 1, added a table for suggested 
Lipid-Lowering agents, and added 
information around caution of using drugs 
that are considered proton pump inhibitors. 
Updated Statistical Analysis Section to align 
with modifications/additions to Protocol 
Amendment 4, including sample size 
determination, planned analyses across 
Phase 2 subgroups. 
Revised Appendix 9 to align with changes 
made to the Schedule of Activities table in 
Phase 2. 
Revised Appendix 10 per modifications made 
to Phase 2 Schedule of Activities table. 
Added Appendix 11 for ALK+ NSCLC 
patients who were treatment-naïve prior to 
receiving PF-06463922 and go on to receive 
crizotinib. 
Adverse Event Reporting and Communication 
of Results by Pfizer language updated to align 
with Pfizer protocol template. 
Minor editorial and clarifications for 
consistency throughout. 
Amendment 3 
29 October 2014 
Clarified that additional doses in Phase 1 may 
be explored outside of the continual 
reassessment method (CRM) model 
recommendations to optimize recommended 
Phase 2 dose (RP2D) determination. 
Increased Phase 1 and Phase 2 sample size. 
Updated Statistical Analysis section to reflect 

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increase in Phase 1 and Phase 2 sample size 
and cover exploration of doses outside of 
CRM model recommendations. 
Added lipid testing to Phase 1 and Phase 2 to 
further evaluate the effect of PF-06463922 on 
cholesterol and triglyceride levels. 
Added a Food Effect Substudy in Phase 1 (up 
to 6 patients) and a corresponding Phase 
1 study objective and endpoint to assess the 
impact of food on PF-06463922 safety and 
pharmacokinetics (PK). 
Added the requirement for a neurological 
assessment in at least 12 Phase 1 patients at 
baseline (and thereafter if clinically indicated) 
to better understand and characterize some of 
the CNS effects observed to date in Phase 1. 
Added that twice daily (BID) dosing will be 
tested in Phase 1 to further characterize and 
evaluate the safety and PK of PF-06463922. 
Changed the requirement from bone scans 
required in all patients at Screening and every 
12 weeks thereafter to bone scans required at 
Screening for all patients and only thereafter 
if bone disease was identified at baseline. 
Additionally, clarified that for patients with 
documented disease progression who are still 
receiving PF-06463922, tumor assessments 
may be done as per standard of care. 
Added a Japanese patient-only Lead-In 
Cohort (LIC) to investigate the safety and PK 
of PF-06463922 in Japanese patients. 
Updated Inclusion Criterion #2 in 
Phase 1 only to additionally allow patients to 
enter the study who have had more than 
2 prior ALK or ROS inhibitors. 
Updated Inclusion Criterion #14 for Japan 
sites only to further define patients not of 
childbearing potential. 

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Removed Exclusion Criterion #11 to avoid 
contradiction to Exclusion Criterion #4. 
Clarified that in those countries where the 
standard of care does not allow for 
treatment-naïve patients to receive 
PF-06463922 in the first-line treatment 
setting, those patients will be excluded from 
EXP-1 and EXP-4 subgroups in Phase 2. 
Added a Cycle 3 Day 1 time point for Blood 
Specimens for Circulating Nucleic Acid 
(CNA) to Phase 2. 
Aligned Study Objectives in Phase 1 and 
Phase 2 with Study Endpoints. 
Removed Screening Blood Metabolite 
Profiling sample collection in Table 4. 
Minor editorial changes made throughout. 
Amendment 2 
28 March 2014 
Minor clarifications and corrections made 
throughout 
Updated Schedule of Activities table in 
Part 1 and Part 2, including PK and PD tables, 
to align with protocol text and study 
objectives, endpoints, and applicable 
appendices. 
Updated Part 2 Study Endpoints to clarify 
efficacy analyses to be performed in 
Phase 1 and Phase 2 to allow an in-depth 
characterization of the efficacy profile in the 
different subpopulations. 
Added the source for the reference document 
being used for midazolam. 
Revised Study Inclusion and Exclusion 
criteria. 
Updated Dose-Limiting Toxicity (DLT) 
definition to clarify that Grade 3 laboratory 
abnormalities do not immediately constitute a 

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DLT, and clarified the criteria for intrapatient 
dose escalation. 
Clarified that midazolam may be evaluated 
with fewer than 3 to 4 dose levels depending 
on emerging PK results from previous dose 
levels evaluated. 
Added new Medication Error section, and 
updated Hospitalization, Exposure During 
Pregnancy, Occupational Exposure and 
Serious Adverse Event Reporting 
Requirements to align with Pfizer’s policy on 
Adverse Event monitoring. 
Updated Communication of Results section to 
align with Pfizer’s policy of Public 
Disclosure. 
Amendment 1 
17 September 2013 
Minor editorial changes made throughout 
Reason for amendment: 
• 
Per US FDA review of the IND, an 
assessment of left ventricular ejection 
fraction (LVEF) was added to ensure safety 
monitoring of any potential LVEF 
dysfunction, and a specific exclusion 
criterion as well as specific DLT definition 
and instructions for dose modification in 
case of toxicity were added to the protocol. 
• 
In addition, the measurement of secondary 
measures of efficacy were added to 
objectives and the endpoints list was 
modified accordingly. 
• 
Finally, minor editorial changes were made 
throughout the protocol to fix some 
inconsistencies. 
Schedule of Activities in Phase 1, Table 1 
• 
Added “LVEF (Echocardiogram or MUGA) 
Assessment at Screening, before dosing at 
Day 1 Cycle 2, before dosing at Day 

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1 Cycle 3, before dosing at Day 1 Cycle 
5 and every two cycles thereafter (ie, before 
dosing at Day 1 Cycle 7, Day 1 Cycle 9, 
etc.), and at the End of Treatment visit 
(±2 days time window applicable at the 
discretion of the investigator).” 
Schedule of Activities in Phase 2, Table 3 
• Added “LVEF (Echocardiogram or 
MUGA) Assessment at Screening, before 
dosing at Day 1 Cycle 2, before dosing at 
Day 1 Cycle 3, before dosing at 
Day 1 Cycle 5 and every two cycles 
thereafter (ie, before dosing at 
Day 1 Cycle 7, Day 1 Cycle 9, etc.), and 
at the End of Treatment visit (±2 days 
time window applicable at the discretion 
of the investigator).” 
• Footnote #24, Banked biospecimen: 
Reduced blood volume collected from 
“6 mL” to “4 ml”, as this is the actual 
volume that will be collected. 
Schedule of Pharmacokinetic Activities in 
Phase 2, Table 4 
• To be consistent with the text in the 
protocol, a row was added to the “MDZ 
Substudy” to include “Blood sample for 
PF-06463922 metabolite profiling” to be 
collected at screening, and at steady-state 
Cycle 1 Day 15: Pre-dose, 0.5, 1, 2, 3, 4, 
6, 8, 9 and 24 hrs post dose. 
Schedule of Pharmacokinetic Activities in 
Phase 1 and Phase 2 
• Updated the Table 2 and Table 4 to match 
Footnote #4 and #7 respectively, to 
indicate the urine sample for all patients 
will be collected at Day 1 Cycle 2. 
Section 1.3.4, Safety Considerations in the 

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Clinical Trial 
• Added “changes in left ventricular ejection 
fraction” to the list of safety observations 
that would be monitored in the study. 
Section 2.1, Study Objectives and 
Section 2.2. Endpoints 
• Added “To assess secondary measures of 
clinical efficacy” as a Secondary 
Objectives in the Phase 2 objectives. 
Section 2.1, Study Objectives and 
Section 2.2. Endpoints 
• Added “Left Ventricular Ejection 
Fraction” to the list of Secondary 
Endpoints. 
• Added “Disease Control Rate (DCR) at 
6 and 12 weeks” to the list of Secondary 
Endpoints in Phase 2 of the study. DCR 
is defined as the percent of patients with a 
confirmed complete response (CR), partial 
response (PR) or stable disease (SD) 
according to RECIST 1.1, at 6 and 
12 weeks, respectively. 
Section 4.2, Exclusion Criteria 
• Added Criteria #22: “Patients presenting 
with abnormal Left Ventricular Ejection 
Fraction (LVEF) by echocardiogram or 
Multi Gated Acquisition Scan (MUGA) 
according to institutional lower limits.” 
Section 3.2 DLT definition (Phase 1) 
Added to “Non Hematologic”: 
• 
A 20% decrease in Left Ventricular 
Ejection Fraction (LVEF) compared to 
baseline echocardiogram or Multi Gated 
Acquisition Scan (MUGA). 
Section 5.2.1, Formulation and Packaging 

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• 
Removed “commercially available” from 
how Midazolam will be supplied, as 
Midazolam will be supplied by the Sponsor. 
• 
Clarified that the prescribed dose of 
Midazolam will be “2 mg/mL”. 
Section 5.2.7, Table 6: PF-06463922 Dose 
Modifications for PF-06463922-Related 
Toxicity 
• Added “LVEF dysfunction” dose 
modification criteria. 
Section 7.1 and Section 7.1.7, Safety 
Assessments 
• Added “In order to monitor potential left 
ventricular ejection fraction dysfunction, 
an echocardiogram or Multi Gated 
Acquisition Scan (MUGA) will be 
performed at the time points described in 
the Schedule of Activities. 
• Changed “patient reported outcomes” to 
“mini mental state examination (MMSE)” 
in the list of safety assessments that will 
be monitored in the study. 
Section 7.5.1, Markers of Drug Response 
• Reduced blood volume collected for the 
blood biospecimen from “6 mL” to 
“4 mL”, as this is the actual volume that 
will be collected. 
Section 9.3, Sample Size Determination, 
Phase 2 
• For clarification of the Phase 2 sample 
size determination, added “If the total 
number of responding patients is equal to 
or greater than 20 for each subpopulation, 
then the null hypothesis will be rejected.” 
Section 9.4.2, Analysis of Secondary 

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Endpoints 
• Added “Disease Control Rate (DCR) at 
6 and 12 weeks” to the list of secondary 
endpoints to be analyzed. Specifically, 
“Disease Control Rate (DCR) is defined 
as the percent of patients with a confirmed 
complete response (CR), partial response 
(PR) or stable disease (SD) according to 
RECIST 1.1, at 6 and 12 weeks, 
respectively. DCR at weeks 6 and 12 will 
be analyzed in the same subpopulations 
described in Section 9.4.1 for ORR.” 
Section 9.6.2, Analysis of Secondary Safety 
Endpoints for Both Phase 1 and Phase 2 
Added “Left Ventricular Ejection Fraction” to 
the list of secondary endpoints to be analyzed. 
Specifically, “For patients with MUGA scans 
or echocardiograms, individual LVEF (left 
ventricular ejection fraction) proportion (%) 
and its changes from baseline will be 
summarized by time point. The number of 
patients and the percentage whose maximum 
decrease from baseline in LVEF is equal or 
greater than 20% will be calculated.” 
Original protocol 
28 June 2013 
N/A 
 
This amendment incorporates all revisions to date, including amendments made at the 
request of country health authorities, institutional review boards/external review boards 
(IRBs/ERBs), etc. 

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PROTOCOL SUMMARY 
INDICATION 
Anaplastic Lymphoma Kinase (ALK)-positive (ALK+) or ROS oncogene 1 (ROS1)-positive 
(ROS1+) advanced non-small cell lung cancer (NSCLC). 
BACKGROUND AND RATIONALE 
PF-06463922 is a selective, ATP competitive small molecule tyrosine kinase inhibitor (TKI) 
of the ALK and ROS1 receptor tyrosine kinases (RTK) that also potently inhibits ALK 
kinase domain mutations responsible for resistance to crizotinib. Oncogenic fusions of ALK 
and ROS1 define two distinct subsets of human lung adenocarcinoma patients and play 
essential roles in regulation of tumor cell survival, growth and metastasis. 
In vitro, PF-06463922 demonstrated potent, concentration-dependent inhibition in catalytic 
activities of ALK, ALK mutants and ROS1 kinases in recombinant enzyme and cell based 
assays. PF-06463922 also inhibited ALK and ROS1 dependent oncogenic functions in 
human NSCLC cell lines, and demonstrated potent and selective growth inhibitory activity 
and induced apoptosis in tumor cell lines exhibiting either non mutant ALK and ROS1 fusion 
variants or mutant ALK fusions that are acquired and resistant to crizotinib treatment. 
In vivo, PF-06463922 demonstrated marked cytoreductive activity in mice bearing tumor 
xenografts that express ALK or ROS1 fusion variants, including the crizotinib resistant 
EML4 ALKL1196M or EML4 ALKG1269A mutations. PF-06463922 treatment 
significantly reduced the tumor size and prolonged animal survival in the orthotopic brain 
models (EML4 ALK and EML4 ALKL1196M) in mice. The anti tumor efficacy of 
PF-06463922 was dose dependent and demonstrated strong correlations to inhibition of ALK 
or ROS1 phosphorylation. The plasma levels associated with inhibitory activity of 
PF-06463922 against EML4 ALKL1196M phosphorylation and anti tumor efficacy in 
EML4 ALKL1196M dependent human NSCLC cell line models was utilized to project target 
human plasma concentrations for clinical studies. 
There remains an unmet medical need to improve ALK+ NSCLC and ROS1+ NSCLC 
patients’ outcomes as no ALK directed compounds so far evaluated have demonstrated 
curative results. Additional drugs are needed to overcome resistance mechanisms, to impact 
patient outcomes through improved response rates and progression free survival (PFS) and 
significant anti-tumor activity on central nervous system (CNS) metastases. 
STUDY OBJECTIVES AND ENDPOINTS 
Phase 1 Portion of the Study 
Primary Objective: 
• To assess safety and tolerability of PF-06463922 as a single agent at increasing dose 
levels in patients with advanced ALK+ or advanced ROS1+ NSCLC in order to 
estimate the Maximum Tolerated Dose (MTD) and select the Recommended 
Phase 2 Dose (RP2D). 

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Secondary Objectives: 
• To evaluate the overall safety and tolerability of PF-06463922. 
• To evaluate the single- and multiple-dose pharmacokinetic (PK) profiles of 
single-agent PF-06463922. 
• To detect early signs of cognitive dysfunction. 
• To evaluate patient reported outcomes (PRO) of global Quality of Life (QOL) 
functioning, and the impact of PF-06463922 on disease/treatment-related symptoms 
of lung cancer. 
• To evaluate the potential of single-agent PF-06463922 to cause CYP3A 
inhibition/induction using midazolam as a probe. 
• To characterize the effects of single-agent PF-06463922 on the QTc interval. 
• To evaluate tumor and blood-based molecular markers of response and resistance to 
single-agent PF-06463922. 
• To characterize the effect of food on PF-06463922. 
• To evaluate preliminary anti-tumor activity of single-agent PF-06463922 in patients 
with advanced ALK+ NSCLC or advanced ROS1+ NSCLC. 
• To evaluate response to prior systemic therapies. 
Exploratory Objectives: 
• To explore the brain penetration of single-agent PF-06463922. 
Phase 2 Portion of the Study 
Primary Objective: 
• To evaluate overall (intra- and extracranial) and intracranial anti-tumor activity of 
single-agent PF-06463922 at RP2D in patients with advanced ALK+ NSCLC or 
advanced ROS1+ NSCLC. 
Secondary Objectives: 
• To confirm the safety and tolerability of single-agent PF-06463922 at the RP2D. 
• To confirm single- and multiple-dose PK profiles of single-agent PF-06463922 at the 
RP2D. 
• To assess secondary measures of clinical efficacy. 

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• To detect early signs of changes in mood, cognitive function, or suicidal ideation and 
behavior (SIB). 
• To evaluate patient reported outcomes (PRO) of global QOL, functioning and the 
impact of PF-06463922 on disease/treatment-related symptoms of lung cancer at the 
RP2D. 
• To further evaluate the effects of single-agent PF-06463922 at the RP2D on the QTc 
interval. 
• To further evaluate tumor and blood-based molecular markers of response and 
resistance to single-agent PF-06463922 at the RP2D. 
• To evaluate the safety and efficacy of single-agent crizotinib following 
PF-06463922 in treatment-naïve patients with advanced ALK+ NSCLC. 
• To evaluate response to prior systemic therapies. 
Exploratory Objectives: 
• To explore the brain penetration of single-agent PF-06463922 at the RP2D. 
Japanese Patient Only Lead-In Cohort (LIC) 
• To evaluate the safety and tolerability PF-06463922 in Japanese Patients before 
starting enrollment of Japanese Patients in Phase 2 portion of the study. 
Drug-drug Interaction (DDI)/Holter Monitoring Study 
• To evaluate the potential of PF-06463922 to inhibit/induce CYP2B6, CYP2C9, P-gp, 
and select Glucuronosyltransferases (UGT) isoforms. 
• To characterize the effects of PF-06463922 on Electrocardiogram (ECG) endpoints. 
• To characterize the safety and efficacy of PF-06463922 of patients entering the 
DDI/Holter monitoring study. 
Endpoints 
Phase 1 Primary Endpoint: 
• Cycle 1 Dose-Limiting Toxicities (DLTs). 
Phase 2 Primary Endpoint: 
• 
Objective tumor response, as assessed by Response Evaluation Criteria in Solid 
Tumor (RECIST) version 1.1 (Appendix 3). In patients with asymptomatic CNS 
metastases, up to five (5) intracranial target lesions in addition to the five (5) 
extracranial target lesions will be assessed.32 

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Secondary Endpoints [all patients unless otherwise indicated]: 
• Adverse Events as characterized by type, frequency, severity (as graded by NCI 
CTCAE v.4.03), seriousness and relationship to study therapy. 
• Laboratory abnormalities as characterized by type, frequency, and severity (as graded 
by NCI CTCAE v.4.03). 
• Left Ventricular Ejection Fraction (LVEF). 
• Vital Signs (heart rate, blood pressure). 
• Total Mini Mental State Examination Score [Phase 1 only]. 
• Mood assessment, Cognitive Function assessment, Suicidal Ideation and Behavior 
assessment [Phase 2 only]. 
• Pharmacokinetic parameters of PF-06463922: Single Dose - Cmax, Tmax, AUClast, 
AUC, CL/F, and Vz/F and t1/2, AUCinf as data permit. Multiple Dose (assuming 
steady-state is achieved) - Css,max, Tss,max, AUCss,, t1/2, Css,min, Css,av, CL/F, Vz/F, Rac 
(AUCss,/AUCsd,) and Rss (AUCss,/AUCsd,inf) as data permit. Phase 1 only: urine PK 
parameters (Ae%, and CLR) of PF-06463922 from MDZ and food effect substudy. 
• Pharmacokinetic parameters of midazolam: Cmax, Tmax, AUClast, CL/F, and Vz/F and 
t1/2, AUCinf as data permit [Phase 1 only]. 
• Patient reported functioning and impact on disease/treatment-related symptoms of 
lung cancer and global QOL. 
• QTc interval. 
• Disease Control Rate (DCR) at 12 and 24 weeks defined as the percent of patients 
with a confirmed complete response (CR), partial response (PR) or stable disease 
(SD) according to RECIST 1.1 at 12 and 24 weeks. 
• 
Objective tumor response, as assessed by Response Evaluation Criteria in Solid 
Tumor (RECIST) version 1.1 (Appendix 3) [Phase 1 only – primary endpoint in 
Phase 2]. In patients with asymptomatic CNS metastases, up to 5 intracranial target 
lesions in addition to the 5 extracranial target lesions will be assessed.32 
• Time-to-event endpoints: Progression-Free Survival (PFS), Overall Survival (OS), 
Duration of Response (DR), and Time to Tumor Response (TTR). 
• Probability of first event being a central nervous system (CNS) progression, non CNS 
progression, or death. Time to Progression (TTP) [Phase 2 only]. 
• Response to prior systemic therapies. 

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• Selected molecular profiling of tumor tissue, eg, ALK kinase domain mutations, and 
Circulating Nucleic Acid (CNA), eg, ALK kinase domain mutations. 
Secondary Endpoints [ALK+ NSCLC Phase 2 patients receiving single-agent crizotinib 
following first-line treatment with PF-06463922]: 
• Adverse Events as characterized by type, frequency, severity (as graded by NCI 
CTCAE v.4.03), seriousness and relationship to study therapy. 
• Laboratory abnormalities as characterized by type, frequency, and severity (as graded 
by NCI CTCAE v.4.03). 
• Objective tumor response, as assessed by Response Evaluation Criteria in Solid 
Tumor (RECIST) version 1.1, and time-to-event endpoints including PFS, DR, TTR 
and OS. 
Phase 1 Exploratory Endpoints: 
• Time to Progression (TTP). 
Phase 1 and 2 Exploratory Endpoints: 
• Cerebral spinal fluid (CSF) concentration of PF-06463922. 
Endpoints for Japanese Patient Only Lead-in Cohort (LIC): 
• Cycle 1 Dose Limiting Toxicities (DLTs). 
Endpoints for Drug-drug Interaction (DDI)/Holter Monitoring Study: 
• Pharmacokinetic parameters (as data permit) for probe substrate after single oral 
administration with or without PF-06463922: Plasma AUC24, AUClast, AUCinf , Cmax, 
Tmax, CL/F, Vz/F and t1/2. 
• Pharmacokinetic parameters (as data permit) for relevant probe substrate 
metabolite(s) and PF-06463922 metabolite(s): Plasma and AUC24, AUClast, AUCinf, 
Cmax, Tmax, t1/2, MRCmax, MRAUCinf, and MRAUClast. 
• PR interval with PF-06463922 treatment. 
STUDY DESIGN 
This is a Phase 1/2, open-label, multicenter, multiple-dose, dose-escalation, safety, PK, 
pharmacodynamic (PD) and anti-cancer efficacy exploration study of PF-06463922 as a 
single agent in patients with advanced ALK+ or ROS1+ NSCLC. This clinical study will 
consist of 2 parts. 

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The Phase 1 portion of the study will estimate the MTD for single-agent PF-06463922 in 
dose escalation cohorts in patients with advanced ALK+ or advanced ROS1+ NSCLC with 
or without asymptomatic CNS metastases, and will enroll approximately 50 patients 
(depending on toxicities observed). Additionally, a food effect substudy will be conducted in 
approximately 6 patients enrolled in Phase 1. 
To understand the single-dose pharmacokinetics (PK) of PF-06463922, a lead-in period 
preceding the continuous daily dosing will be conducted. To evaluate the effect of 
PF-06463922 on CYP3A inhibition/induction, a midazolam (MDZ) drug-drug interaction 
(DDI) substudy will be conducted at 3 to 4 PF-06463922 dose levels in Phase 1 (fewer dose 
levels may be evaluated depending on emerging PK results). During the study, real-time 
pharmacokinetic monitoring will be conducted as much as possible. 
The Phase 2 portion of the study will evaluate the anti-cancer activity of single-agent 
PF-06463922 in multiple subpopulations of patients with advanced ALK+ NSCLC and 
patients with advanced ROS1+ NSCLC and will allow to better define the safety, PK and 
pharmacodynamic profiles of single-agent PF-06463922 at the RP2D. Additionally, at the 
discretion of the treating investigator and if clinically indicated, patients who are ALK 
inhibitor treatment naïve at baseline (ie, part of EXP-1 subpopulation) and who discontinue 
PF-06463922 due to reasons other than withdrawal of consent may be eligible to receive 
single-agent crizotinib. At the time of PF-06463922 discontinuation, patients who are 
eligible to receive crizotinib will undergo a brief Screening period to ensure inclusion and 
exclusion criteria are met and required assessments are performed. 
To evaluate the safety and tolerability of PF-06463922 in Japanese patients, a Japanese 
patient-only lead-in cohort (LIC) will be enrolled to examine the safety and PK of 
PF-06463922 at a previously tested dose in Phase 1. The LIC will be conducted at Japanese 
sites concurrently with the Phase 2 portion of the study but will be considered separate from 
the Phase 2 enrollment. Japan will participate in Phase 2 after completion (DLT evaluation) 
of LIC. Patients enrolled into the LIC will follow the same eligibility criteria, study 
procedures (unless otherwise specified) and discontinuation criteria as outlined in Phase 2. 
Initially up to 3 patients will be enrolled and treated. If a DLT is observed in 1 of the initial 
3 treated patients, 3 additional patients to a total of 6 will be enrolled and treated. Additional 
patients may be enrolled depending on the overall safety and PK profile. 
To evaluate the potential interaction of PF-06463922 on drugs that are metabolized or 
transported via pathways that include CYP2B6, CYP2C9, P-gp, and select UGT isoforms, a 
drug-drug interaction (DDI) study will be conducted in approximately 30 (6 evaluable for 
each probe substrate) patients who meet the prior treatment requirements of EXP groups 2-6. 
Additionally, within this study, an evaluation of the effects of PF-06463922 on the PR 
interval will be conducted via continuous Holter telemetry comparing the subject’s 
time-matched PR interval (approximately 10 points) with exposure of 
PF-06463922 following a single dose and again at steady state. In addition, arrhythmia 
analysis will be performed in these patients and these data will be analyzed separately from 
Phase 2 data. This study will be conducted in approximately 10 participating Phase 2 sites 
and will begin and conclude upon official notification by the sponsor via letter or email. 

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The Phase 2 portion will enroll approximately 260 patients and will include patients from the 
following subpopulations: 
• EXP-1: Treatment-naïve patients with advanced ALK+ NSCLC with or without 
asymptomatic CNS metastases (targeting 30 patients). No prior chemotherapy is 
allowed in the metastatic setting. In those countries where standard of care does not 
allow for ALK+ NSCLC treatment-naïve patients to receive PF-06463922 in the 
first-line treatment setting, patients will not be enrolled in EXP-1 subgroup. 
EXP-1 patients may be eligible to receive single-agent crizotinib following treatment 
with PF-06463922 if allowed per local guidelines and appropriate per investigator 
discretion. 
• EXP-2: Patients with advanced ALK+ NSCLC with or without asymptomatic CNS 
metastases relapsing after only crizotinib therapy (targeting 80 patients between 
EXP-2 and EXP-3A-EXP-3B combined). No prior chemotherapy is allowed in the 
metastatic setting. 
• EXP-3: Patients with advanced ALK+ NSCLC with or without asymptomatic CNS 
metastases relapsing after crizotinib therapy and 1 or 2 prior regimens of 
chemotherapy given before or after crizotinib therapy [EXP-3A]; OR patients with 
advanced ALK+ NSCLC with or without asymptomatic CNS metastases relapsing 
after 1 ALK inhibitor therapy other than crizotinib with or without any number of 
prior chemotherapy regimens in any disease setting [EXP-3B] (as above, targeting 
80 patients between EXP-2 and EXP-3A-EXP-3B combined). 
• EXP-4: Patients with advanced ALK+ NSCLC with or without asymptomatic CNS 
metastases relapsing after 2 prior lines of ALK inhibitor therapies (targeting 
70 patients). Patients may have had any number of prior chemotherapy regimens in 
any disease setting. 
• EXP-5: Patients with advanced ALK+ NSCLC with or without asymptomatic CNS 
metastases relapsing after 3 prior lines of ALK inhibitor therapies (targeting 
40 patients). Patients may have had any number of prior chemotherapy regimens in 
any disease setting. 
• EXP-6: Patients with advanced ROS1+ NSCLC who are treatment naïve or have had 
any number of prior therapies (targeting approximately 40 patients). Patients may or 
may not have asymptomatic CNS metastases. In those countries where standard of 
care does not allow for ROS1+ NSCLC treatment-naïve patients to receive 
PF-06463922 in the first-line treatment setting, patients will not be enrolled in 
EXP-6 treatment-naïve subgroup. 
Approximately 340 patients (Phase 1, Phase 2, and DDI and Holter monitoring study) are 
expected to be enrolled in the study overall. 

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After the collection of data for the evaluation of primary objective is completed, and most of 
the secondary endpoints characterized, data recording will be limited to adverse events, with 
the purpose of performing long term safety assessments and overall survival. At the end of 
treatment the biological samples will be collected for translational analysis. 
Guidance on the management of patients on study is provided to investigators in Table 1. 
The revised schedule of activities will allow the investigators to perform most study tests and 
procedures per standard of care or clinical judgement. 
STUDY TREATMENT 
The starting dose for PF-06463922 in the Phase 1 will be 10 mg administered once daily (or 
twice daily [BID] dosing) in 21-day cycles. When BID dosing is used, the choice of BID 
dose levels will be evaluated based on emerging safety and PK data. Patients in the 
Phase 2 will receive PF-06463922 as a single agent at the RP2D of 100 mg once daily (QD) 
in 21-day cycles. 
For patients participating in the MDZ DDI study in Phase 1, PF-06463922 will be 
administered with MDZ on Cycle 1 Day 15. In the MDZ interaction sub-study, patients will 
receive a single 2 mg oral dose of MDZ on Day -7 and will receive another single 2 mg oral 
dose of MDZ concurrently with PF-06463922 on Cycle 1 Day 15 (morning dose if on BID 
dosing schedule). 
For patients participating in the food effect study in Phase 1, PF-06463922 will be 
administered following an overnight fast of at least 10 hours on Cycle 1 Day -7 and 
Cycle 1 Day 1. 
For patients participating in the DDI and Holter monitoring part of the study, patients will be 
administered a dose of probe substrate alone in the fasted state when possible (no food 
2 hours before through 2 hours after dosing of probe substrate) on Day -2, and then starting 
on Cycle 1 Day 1, patients will begin daily dosing of 100 mg QD PF-06463922. On 
Cycle 1 Day 15, another single dose of the probe substrate will be administered in the fasted 
state when possible (no food 2 hours before through 2 hours after dosing of probe substrate) 
concurrently with PF-06463922. Twenty-four Holter monitoring will be conducted on 
Day -1 through Cycle 1 Day 1 and again on Cycle 1 Day 14. On Day -1, the 24-hour Holter 
monitoring will begin approximately 24 hours after probe substrate administration on Day -2. 
In all study parts, patients will continue with the study treatment until progression of disease 
as determined by the investigator, unacceptable toxicity, death or consent withdrawal. 
Patients may continue PF-06463922 treatment after objective progression of disease is 
determined if the patient is continuing to experience clinical benefit, in the opinion of the 
investigator, and after discussion with the Sponsor. 

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SCHEDULE OF ACTIVITIES 
The Schedule of Activities (SOA) 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. 
Upon approval of Amendment 8, study activities will be reduced as described in Table 1. 
The investigator may schedule visits (unplanned visits) in addition to those listed in the 
Schedule of Activities in order to conduct evaluations or assessments required to protect the 
well-being of the patient. 
The SOA for each of the two study sections and the Japanese patient-only LIC are separately 
reported in the Tables and Appendix below. 
Table 1 reduced schedule of assessments upon approval of Amendment 8. 
Table 2 and Table 3 for the Phase 1 Portion of the Study. 
Table 4 and Table 5 for the Phase 2 Portion of the Study. 
Table 6 for the Drug-Drug Interaction and Holter Monitoring Study Requirements 
Appendix 9 for Japanese patient-only LIC. 
Appendix 11 for patients receiving Crizotinib post PF-06463922. 

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SCHEDULE OF ACTIVITIES 
Table 1. 
Reduced Schedule of Assessments upon approval of Amendment 8 
 
Study Treatment1 
Protocol Activity 
Visits on Day 1 of Every Other Cycle 
End of Treatment12 
Follow- Up13 
Visit or Assessment 
Window (days) Unless 
Otherwise Noted 
±4 days 
2 days 
±7 days 
Contraceptive check (as 
appropriate)2 
X (every cycle 2 days) 
X 
X 
Laboratory 
Pregnancy test3 
X (every cycle 2 days) 
X 
X 
For France and Germany 
only: Transthoracic 
echocardiogram to assess 
PAP and right heart function4 
Every 24 weeks 
±2 weeks 
X 
Study Treatment 
PF-06463922 Treatment5 
Once a day continuously 
Tumor Assessments 
CT and MRI Scan or 
Equivalent6 
As per local clinical practice 
Other Clinical Assessments 
Adverse Events7 
X 
X 
X 
Survival Follow-up 
X 
Other Samples 
De Novo Tumor Specimens8 
‘X’ 
Blood Specimens for 
Circulating Nucleic Acid 
(CNA) Profiling9 
X 
Cerebrospinal fluid (CSF) 
PF-06463922 concentration 
(optional)10 
Any time during steady state, ideally 
4-6 hours and 8-9 hours post-dose 
Blood sample (whenever 
CSF for PF-06463922 is 
collected)11 
Same time as CSF 
PF-06463922 concentration sample 
collected 

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1. 
All assessments should be performed prior to dosing with study medications unless otherwise indicated. All cycles are 3 weeks in duration (±2 days). Sufficient study 
medication for 2 cycles of treatment will be dispensed at each clinic visit. The Investigator is responsible for informing the patient to contact the clinical site in case of any 
adverse events. 
2. 
Contraceptive check: patient may be contacted by phone to confirm contraception is still appropriate per the protocol. Males and females of childbearing potential must be 
contacted post-study to ensure that they continue to use appropriate contraception for at least 97 and 21 days, respectively, after the last dose of study drug. 
3. 
Serum Pregnancy Test: Pregnancy tests will be routinely repeated at every cycle (±2 days) during the active treatment period, at the end of study therapy (± 2 days), at first 
follow-up visit (± 7 days), and additionally whenever one menstrual cycle is missed or when potential pregnancy is otherwise suspected. Additional pregnancy tests may also 
be undertaken if requested by IRB/IECs or if required by local regulations. The pregnancy test should be performed at the clinical site’s local laboratory. Where that is not 
possible, patients will provide the laboratory test results carried out at a non-clinical site laboratory, eg, by telephone, and bring a copy of the laboratory test results at the next 
cycle visit. The copy of the laboratory test results must be retained in the patient’s file at the clinical site for documentation purposes. 
4. 
For sites in France and Germany, a transthoracic echocardiogram (TTE) will be performed every 6 months (±2 weeks) during treatment, and only at the End of Treatment 
visit if the previous assessment was >1 month. Pulmonary arterial pressure (PAP) will be assessed. 
5. 
Study Treatment: described in the Study Treatments section. 
6. 
Tumor Assessments: Will be repeated at the frequency as per local clinical practice, tumor assessment information should be retained in the patient’s file for documentation 
purposes 
7. 
Adverse Event (AE) Assessments: Adverse events should be documented and recorded at each visit using NCI CTCAE version 4.03. Patients must be followed for AEs for 
28 days after the last treatment administration or until all drug related toxicities have resolved, whichever is later; or earlier than 28 days should the patient commence another 
anti-cancer therapy in the meantime. For SAEs, the active reporting period to Pfizer or its designated representative begins from the time that the patient provides informed 
consent, which is obtained prior to the patient’s participation in the study, ie, prior to undergoing any study-related procedure and/or receiving investigational product, through 
and including 28 calendar days after the last administration of the investigational product. Serious adverse events occurring to a patient after the active reporting period has 
ended should be reported to the Sponsor if the investigator becomes aware of them; at a minimum, all serious adverse events that the investigator believes have at least a 
reasonable possibility of being related to study drug are to be reported to the Sponsor. 
8. 
De Novo Tumor Specimens: Optional de novo tumor biopsy at the time of progression is strongly encouraged for all patients enrolled in the study. If present, pleural 
effusion (PE) cell pellet may substitute for tumor core biopsy, as appropriate. Fine needle aspiration (FNA) samples (2-3 pathes prepared as FFPE cell block) are not 
preferred and should only be performed in the event a biopsy or pleural effusion cell pellet is not safe or feasible. If local country regulations do not allow for tissue block to 
be submitted, 5-micron FFPE tumor tissue slides (at least 12 slides) are acceptable. Tissue specimens from all patients will be used for additional biomarker analyses. Details 
for handling of these specimens including processing, storage, and shipment will be provided in the Study Manual 
9. 
Blood Specimens for Circulating Nucleic Acid (CNA) Profiling: 10 mL blood specimen optimized for plasma preparation for nucleic acid analysis (eg, circulating free 
DNA (cfDNA) or RNA (cfRNA)) will be collected at End of Treatment. Details for handling of these specimens including processing, storage, and shipment will be provided 
in the Study Manual. 
10. CSF PF-06463922 Concentration Sample (Optional): If a patient undergoes a lumber puncture, a sample of CSF should be collected for exploratory analysis of 
PF-06463922 concentration, if possible. If this CSF sample is collected, a blood sample for PK analysis should also be collected at approximately the same time as the CSF 
sample. If scheduling permits, one CSF sample should be taken between 4 and 6 hours post dose. If it is possible to take a second sample, collection should be between 8 and 
9 hours post-dose. 
11. If a CSF PF-06463922 concentration sample is collected, a blood sample for PK analysis should be collected at approximately the same time as the CSF sample. 
12. End of Treatment Visit: Obtain these assessments if not completed in the last week. For patients who receive crizotinib following treatment with PF-06463922, assessments 
at the End of Treatment visit are according to Appendix 11. 

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13. Follow up: At least 28 days, and no more than 35 days after discontinuation of treatment patients will return to undergo assessment for resolution of any treatment-related 
toxicity, and pregnancy test for female patients. 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. After study discontinuation the 
survival follow-up will be performed every 2 months and will include also the collection of information on subsequent anticancer therapies (telephone contact is acceptable). 

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Table 2. 
Phase 1 Portion of the Study 
Note: The current table is no longer applicable after the approval of Amendment 8 
 
CYCLE 1 
(21 days) 
CYCLE 2 
(21 days) 
CYCLES 
3- 25 (Up to 
Month 18) 
(21 days) 
CYCLES 
>25 (Months 
˃18) 
(21 days) 
Protocol Activity 
Screening 
1 
(28 days) 
Lead-in 
PK 
(Day -7) 
Day 1 
Day 8 
Day 15 
Day 1 
Day 1 
Day 1 of Every 
Other Cycle 
End of 
Treatment27 
Follow- Up26 
Visit Window (days) 
N/A 
+1 
1 
1 
1 
2 
2 
±2 
2 
±7 
Informed consent2 
X 
Tumor history 
X 
Medical history 
X 
Physical examination 
including weight 
X 
(X) 
(X) 
X 
X 
X 
Baseline signs and 
symptoms3 
X 
X 
Height 
X 
Weight 
X 
X 
X 
X 
X 
Vital signs4 
X 
X 
X 
X 
X 
X 
X 
X 
Performance status5 
X 
X 
X 
X 
X 
X 
Laboratory 
Hematology6 
X 
(X) 
X 
X 
X 
X 
X 
Blood Chemistry7 
X 
(X) 
X 
X 
X 
X 
X 
Coagulation8 
X 
(X) 
X 
Lipids9 
X 
(X) 
X 
X 
X 
X 
X 
Urinalysis10 
X 
(X) 
X 
Pregnancy test11 
X 
X 
(X) 
X 
X 
X 
X 
(12-lead) ECG12 
X 
X 
X 
X 
X 
X 
X 
X 
LVEF Assessments 
(Echocardiogram or 
MUGA)28 
X 
X 
X 
Every 4 Cycles 
X 

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CYCLE 1 
(21 days) 
CYCLE 2 
(21 days) 
CYCLES 
3- 25 (Up to 
Month 18) 
(21 days) 
CYCLES 
>25 (Months 
˃18) 
(21 days) 
Protocol Activity 
Screening 
1 
(28 days) 
Lead-in 
PK 
(Day -7) 
Day 1 
Day 8 
Day 15 
Day 1 
Day 1 
Day 1 of Every 
Other Cycle 
End of 
Treatment27 
Follow- Up26 
Visit Window (days) 
N/A 
+1 
1 
1 
1 
2 
2 
±2 
2 
±7 
For France and Germany 
only: Transthoracic 
echocardiogram to assess 
PAP and right heart 
function30 
Every 6 months 
±2 weeks 
Every 6 months 
(±2 weeks) 
X 
Registration and 
Treatment 
Registration13 
X 
PF-06463922 Treatment14,15 
X 
Once a day or twice a day, continuously 
Midazolam Treatment for 
patients participating in the 
midazolam sub-study16 
X (MDZ 
only) 
X 
Tumor Assessments 
CT and MRI Scan or 
Equivalent17 
X 
X and then 
every 6 weeks 
1 week 
Every 12 weeks 
±1 week 
(X) 
Cerebrospinal Fluid18 
X 
X 
X 
Other Clinical 
Assessments 
Adverse Events19 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant Medications 
and non-drug supportive 
interventions20 
X 
X 
X 
X 
X 
X 
EORTC QLQ-C30, 
QLQ-LC1325 
X 
X 
X 
X 
X 
Neurological exam29 
X 
Only as clinically indicated 
Survival Follow-up 
X 
Other Samples 

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CYCLE 1 
(21 days) 
CYCLE 2 
(21 days) 
CYCLES 
3- 25 (Up to 
Month 18) 
(21 days) 
CYCLES 
>25 (Months 
˃18) 
(21 days) 
Protocol Activity 
Screening 
1 
(28 days) 
Lead-in 
PK 
(Day -7) 
Day 1 
Day 8 
Day 15 
Day 1 
Day 1 
Day 1 of Every 
Other Cycle 
End of 
Treatment27 
Follow- Up26 
Visit Window (days) 
N/A 
+1 
1 
1 
1 
2 
2 
±2 
2 
±7 
Archival Tumor Tissue 
Specimen21 
X 
De Novo Tumor 
Specimens22 
‘X’ 
‘X’ 
Blood Specimens for 
Circulating Nucleic Acid 
(CNA) Profiling23 
X 
X 
Banked Biospecimen24 
X 
Footnotes (X) refer to specific footnote when the measurement may be optional /repeat measurement might not be required. 
1. 
Screening: To be obtained within 28 days prior to registration. 
2. 
Informed Consent: Must be obtained prior to undergoing any study-specific procedures. 
3. 
Baseline Signs & Symptoms: Patients will be asked about any signs and symptoms experienced within the 14 days prior to study entry. Worsening of baseline signs and 
symptoms will be recorded on the Adverse Events CRF page. 
4. 
Vital Signs: Blood pressure and pulse rate to be recorded in sitting position. 
5. 
Performance Status: use ECOG – see Appendix 4. 
6. 
Hematology: No need to repeat on C1D1 if baseline assessment performed within 7 days prior to that date. See Assessments section for Laboratory Tests in Appendix 1. 
7. 
Blood Chemistry: No need to repeat on C1D1 if baseline assessment performed within 7 days prior to that date. See Assessments section for Laboratory Tests in 
Appendix 1. 
8. 
Coagulation: No need to repeat on C1D1 if baseline assessment performed within 7 days prior to that date. See Assessments section for Laboratory Tests in Appendix 1. 
9. 
Lipids: No need to repeat on C1D1 if baseline assessment performed within 7 days prior to that date. See Assessments section for Laboratory Tests in Appendix 1. 
10. Urinalysis: Dipstick is acceptable. Microscopic analyses if dipstick abnormal. No need to repeat on C1D1 if baseline assessment performed within 7 days prior to that date. 
See Assessments section for Laboratory Tests in Appendix 1. 
11. Serum Pregnancy Test: For female patients of childbearing potential, a serum or urine pregnancy test, with sensitivity of at least 25 mIU/mL, will be performed on two 
occasions prior to starting study therapy - once at the start of screening and once at the baseline visit, immediately before investigational product administration. Adequate 
contraception (2 forms as described in the protocol) must be initiated after the first negative pregnancy test is obtained at screening. Pregnancy tests will also be routinely 
repeated at every cycle during the active treatment period (every other Cycle beyond 18 months), at the end of study therapy and additionally whenever one menstrual cycle is 
missed or when potential pregnancy is otherwise suspected. Additional pregnancy tests may also be undertaken if requested by IRB/IECs or if required by local regulations. 

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12. Triplicate 12-lead ECGs: At each time point, 3 consecutive 12-lead ECGs will be performed approximately 2 minutes apart to determine mean QTc interval. ECGs will be 
collected as follows: a) at Screening, b) Day -7 (Lead-in) after single-dose administration at pre-dose, at projected Cmax (1 hr), and at 4 hrs post-dose, c) Cycle 1 Day 1, Day 8, 
and Day 15 at pre-dose (0 hour) and 1 hours post-dose. For Cycles 2-5, 1 hr post-dose (time matched with PK), and d) End of Treatment. In addition to these time points, 
ECGs should be repeated as clinically indicated. Additional ECG time points may be included based on the emerging data. 
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 (501 msec), the ECGs should be re-evaluated by a qualified person at the institution for confirmation. Additional triplicate 
ECGs may be performed as clinically indicated. All ECG assessments should be matched with a PK sample. 
13. Registration: patient number and dose level allocation operated by Pfizer Inc. Registration will be within 2 days prior to lead-in single dose as appropriate. 
14. Trial Treatment: described in the Study Treatments section. 
15. Lead-in PF-06463922 Dose: A single dose of PF-06463922 will be given on Day –7 (lead-in period) for all patients in the Phase 1 except the patients who are scheduled for 
the midazolam (MDZ) interaction substudy. The timing of the lead-in dose may be modified based on PK data obtained. 
16. Midazolam (MDZ) Treatment: For patients who are scheduled for the MDZ interaction substudy only. A single 2-mg oral dose of MDZ will be given on Day –7 and 
Cycle 1 Day 15. On Cycle 1 Day 15, MDZ will be given concurrently with PF-06463922. Patients participating in the MDZ substudy will NOT receive any lead-in dose of 
PF-06463922 on Day -7. 
17. Tumor Assessment: Tumor assessments will include all known or suspected disease sites. CT or MRI scans of Chest Abdomin Pelvis [CAP] and MRI of the brain will be 
performed at screening. Gadolinium contrast enhanced MRI must be used for assessment of CNS lesions with contingent slices of 1 mm for lesions 5 mm – 10 mm in size, 
5 mm for lesions greater than 10 mm. Bone scans (or bone MRI if preferred by investigator) will be performed at baseline for all patients and repeated every 12 weeks on 
study only if evidence of bone metastases are observed at baseline. For all tumor assessments, the method of assessment that was used at baseline should be the same method 
used throughout the study. For patients who are without documented disease progression, CT and MRI scans to be done every 6 weeks 1 week up to approximately 
18 months, and then every 12 weeks ±1 week beyond 18 months,and responses to be confirmed 4 weeks later (RECIST v1.1) until documented progression of disease. For 
patients with bone involvement at Screening, CT or MRI or other appropriate imaging for bone assessment will be done every 6 weeks 1 week up to approximately 
18 months, and then every 12 weeks ±1 week beyond 18 months (in addition to the every 12 week bone scan or bone MRI for detection of new disease) and responses will be 
confirmed 4 weeks later (RECIST v1.1) until documented progression of disease. For patients who have documented disease progression but are still receiving 
PF-06463922, CT and MRI scans are to be done according to local institutional standard of care. Every effort should be made to maintain the assessment scheduling relative 
to Cycle 1 Day 1 especially if there are dosing cycle interruptions due to toxicities. Tumor assessment should be repeated at the end of treatment visit if more than 6 weeks 
(more than 12 weeks beyond 18 months) have passed since the last evaluation. CSF sampling in patients with asymptomatic leptomenigeal disease/carcinomatous meningitis 
(LM/CM) will be performed at baseline, and if clinically safe and feasible, further CSF cytology will be performed on study every 2 cycles of treatment (every 12 weeks 
beyond 18 months) to assess disease. 
18. Cerebrospinal Fluid (CSF): CSF is mandatory for patients who have asymptomatic radiologically suspected leptomeningeal disease (LM) or carcinomatous meningitis (CM) 
but negative spinal fluid. CSF will be collected at baseline and on study to determine PF-06463922 concentrations. A blood sample for PK analysis should also be collected 
at approximately the same time as the post-dose CSF sample. 
19. Adverse Event (AE) Assessments: Adverse events should be documented and recorded at each visit using NCI CTCAE version 4.03. Patients must be followed for AEs for 
28 days after the last treatment administration or until all drug related toxicities have resolved, whichever is later; or earlier than 28 days should the patient commence another 
anti-cancer therapy in the meantime. For SAEs, the active reporting period to Pfizer or its designated representative begins from the time that the patient provides informed 
consent, which is obtained prior to the patient’s participation in the study, ie, prior to undergoing any study-related procedure and/or receiving investigational product, through 
and including 28 calendar days after the last administration of the investigational product. Serious adverse events occurring to a patient after the active reporting period has 
ended should be reported to the Sponsor if the investigator becomes aware of them; at a minimum, all serious adverse events that the investigator believes have at least a 
reasonable possibility of being related to study drug are to be reported to the Sponsor. 
20. Concomitant Medications and Non-Drug Supportive Interventions: All concomitant medications and non-drug supportive interventions should be recorded in the CRF. 

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21. Archival Tumor Tissue Specimen: All patients will provide a formalin-fixed paraffin embedded (FFPE) archival tumor specimen, specifically a FFPE tissue block that 
contain sufficient tissue to generate at least 6 (preferably 12) unstained slides, each with tissue sections that are 5 microns thick, or at least 6 (preferably 12) unbaked glass 
slides, each containing an unstained 5 micron FFPE tissue section if FFPE tissue block cannot be submitted. If an archival tumor tissue sample is not available, a de novo 
tumor specimen must be obtained. Specimens will be sent to the Sponsor-designated central laboratories for assessment of biomarkers potentially associated with sensitivity 
and/or resistance to PF-06463922 (eg, ALK mutations, mutations/copy number variation of candidate genes, expression and/or phosphorylation of candidate proteins, etc); for 
ROS1+ NSCLC patients specimens will be sent to the Sponsor-designated central laboratory for ROS1 status confirmation. 
22. De Novo Tumor Specimens: Optional de novo tumor biospy at screening and at the time of progression is encouraged. If present, pleural effusion (PE) cell pellet may 
substitute for tumor core biopsy, as appropriate. Fine needle aspiration (FNA) samples (2-3 pathes prepared as FFPE cell block) are not preferred and should only be 
performed in the event a biopsy or pleural effusion cell pellet is not safe or feasible. If local country regulations do not allow for tissue block to be submitted, 5-micron FFPE 
tumor tissue slides (at least 12 slides) are acceptable. In all cases, this specimen will be provided in addition to the archival tumor tissue specimen that is required for 
enrollment. Tissue specimens from all patients will be used for additional biomarker analyses. Details for handling of these specimens including processing, storage, and 
shipment will be provided in the Study Manual. 
23. Blood Specimens for Circulating Nucleic Acid (CNA) Profiling: 10 mL blood specimen optimized for plasma preparation for nucleic acid analysis (eg, circulating free 
DNA (cfDNA) or RNA (cfRNA)) will be collected at screening and at end of treatment. Details for handling of these specimens including processing, storage, and shipment 
will be provided in the Study Manual. 
24. Banked Biospecimen: Unless prohibited by local regulations, a blood specimen (Prep D1: 4 mL K2 EDTA whole blood collection optimized for DNA analysis), retained for 
pharmacogenomic analyses, will be collected at screening. 
25. EORTC QLQ-C30 and QLQ-LC13: Patients must complete all EORTC QLQ-C30 and QLQ-LC13 self-assessment questionnaires in the clinic at the specified time points 
prior to dosing. At Day -7 (lead- in period) site staff (eg, site coordinators) should instruct patients that the assessment should be completed without help from friends or 
family members and also recommend that this assessment be completed in the morning. All scheduled assessments of the EORTC QLQ-C30 and QLQ LC13 cannot be taken 
home and must be completed in the clinic prior to any other study or medical procedures. 
26. Follow up: At least 28 days, and no more than 35 days after discontinuation of treatment 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. Patients discontinuing 
treatment for reasons other than progression of disease will continue to perform tumor assessments until PD or a new anti-cancer therapy is commenced. Survival followup 
every 2 months after PD or new anti-cancer therapy has commenced will be performed (telephone contact is acceptable). 
27. End of Treatment Visit: Obtain these assessments if not completed in the last week (last 6 weeks for tumor assessments if during the first 18 months, then last 12 weeks if 
beyond month 18). 
28. LVEF Assessments: Echocardiogram or MUGA to be performed at Screening, before dosing at Day 1 Cycle 2, before dosing at Day 1 Cycle 3, before dosing at Day 1 Cycle 
5 and every two cycles thereafter (ie, before dosing at Day 1 Cycle 7, Day 1 Cycle 9, etc.) up to approximately 18 months, and then every 4 cycles thereafter, and at the End 
of Treatment visit (2 days time window applicable at the discretion of the investigator). The same method should be used at each time point. 
29. Neurological Examination: A neurological examination by a licensed neurologist may be conducted in at least 12 patients in Phase 1 at baseline and, if clinically indicated, 
at any time point thereafter. 
30. For sites in France and Germany, a transthoracic echocardiogram (TTE) will be performed every 6 months (±2 weeks) during treatment, and only at the End of Treatment visit 
if the previous assessment was >1 month. Pulmonary arterial pressure (PAP) will be assessed. 

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Table 3. 
Phase 1 Portion of the Study Pharmacokinetic Assessments 
Note: After cycle 5, PK samples collection is not required anymore, except for CSF sample collection as detailed on Footnote 9 
 
CYCLE 1 
(21 days) 
CYCLE 2-5 
(21 days) 
Protocol Activity 
Screen 
(28 days) 
Lead-in PK 
(Day -7) 
Day 1 
Day 8 
Day 15 
Day 1 
Visit Window 
N/A 
+1 
1 
1 
1 
2 
All patients 
Plasma sampling for full PF-06463922 PK in patients not 
participating in the MDZ or the food effect substudy1 
X 
X 
X 
X 
X 
MDZ Substudy 
Plasma sampling for full PF-06463922 PK in patients 
participating in the MDZ substudy2 
X 
X 
X 
X 
Plasma sampling for full MDZ PK3 
X 
X 
Food Effect Substudy 
Blood sample for PF-06463922 in Food Effect Study4 
X 
X 
X 
X 
X 
Blood sample for PF-06463922 metabolite profiling5 
X 
24-hour urine collection for PF-06463922 PK6 
X 
All Patients 
Urine Sample for 6 beta-hydroxycortisol/cortisol 
(6-OHC/C) ratio7 
X 
X 
X 
X 
X (Cycle 2 only) 
4-hydroxycholesterol/ Cholesterol 
Blood Sample8 
X 
X 
X 
X 
X 
Cerebrospinal fluid for PK concentration (optional)9 
Anytime at steady state 
Footnotes 
 
1. 
PF-06463922 PK Sampling: Blood samples will be collected for PK sampling on the following days 1) Day-7 (Lead-in) Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24, 48, 72, 96 and 
120 hours post dose (two samples between 48 to 120 hrs). 2) Cycle 1 Day 1 and Day 8 at pre-dose, 1 hour and 4 hours post dose, 3) Cycle 1 Day 15: Pre-dose, 0.5, 1, 2, 3, 4, 
6, 8, 9 and 24 hours. For patients on BID dosing, the 24-hour time point sample need not be collected. 4) Day 1 of Cycles 2 to 5: Pre-dose and 1 hour post dose (time 
matched with ECG). 
2. 
PF-06463922 PK Sampling for patients who participate in the MDZ interaction substudy: Blood samples will be collected on Cycle 1 Day 1 and Cycle 1 Day 15 at 
pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post dose. On Cycle1 Day 8, a blood sample will be collected at pre-dose, 1 and 4 hours post-dose. Cycles 2-5: Pre-dose and 
1 hour (time matched with ECG). 
3. 
MDZ PK Samples: In MDZ interaction substudy, a PK profile of MDZ will be collected after a single oral MDZ dose on Day –7 (lead-in period) and Cycle 1 Day 15 at the 
following time points: 0 (pre-dose), 0.5, 1, 2, 4, 6, 8, 9, and 24 hours post dose. 

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4. 
Food-Effect Substudy: PK samples will be collected on Day -7 at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24, 48, 72, 96, and 120 hrs post dose (2 samples between 48 to 120 hrs) and 
Cycle 1 Day 1 at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, and 24 hrs post-dose. For patients on BID dosing, the 24 hour time point sample need not be collected. Each patient will 
serve as their own control in which PF-06463922 will be administered in the morning under either “fed” or “fasted” conditions on Day (-7) and Day 1 of Cycle 1. PK samples 
after Cycle 1 Day 1 will follow same schedule as footnote (1). The testing order for fed versus fasted conditions will be as follows: The first half of the patients in this 
substudy will be tested under fed followed by fasted conditions and the second half of the patients will be tested under fasted followed by fed conditions. 
5. 
Blood Sample for PF-06463922 Metabolite Profiling: Metabolite profiling will be conducted in the food effect cohort for all patients. Blood samples will be collected at 
steady-state on Cycle 1 Day 15: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hrs post-dose. 
6. 
Urine for PF-06463922 PK: Urine will be collected for 24 hrs after PF-06463922 dosing on Cycle 1 Day 15 from food effect cohorts over the following intervals: 0 to 4 hrs, 
4 to 12 hrs and 12 to 24 hrs post-dose. For patients on BID dosing, 12-24-hour post-dose urine collection is not required. 
7. 
Urine Sample for 6 beta-hydroxycortisol/cortisol (6-OHC/C) ratio: Morning urine sample (pre-dose) will be collected on Day-7, Day 1 of Cycle 1, Day 8 & 15 of 
Cycle 1 and Day 1 of Cycle 2. 
8. 
Blood Sample for 4-hydroxycholesterol/Cholesterol: Blood sample will be collected at pre-dose on Day-7, Cycle 1 Day 1, Cycle 1 Day 8, Cycle 1 Day 15, Cycles 2 to 
5 Day 1. 
9. 
CSF Sample (Optional): If a patient undergoes a lumber puncture, a sample of CSF should be collected for exploratory analysis of PF-06463922 concentration, if possible. 
If this CSF sample is collected, a blood sample for PK analysis should also be collected at approximately the same time as the CSF sample. 

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Table 4. 
Phase 2 Portion of the Study 
Note: The current table is no longer applicable after the approval of Amendment 8 
 
CYCLE 1 
(21 days) 
CYCLE 2 
(21 days) 
CYCLES 3 – 
38 (Up to Month 
30) 
(21 days) 
CYCLES 
>38 (Months 
>30) 
(21 days) 
Protocol Activity 
Screen1 
(28 days) 
Lead-in 
PK 
(Day -7) 
Day 1 Day 8 
Day 15 
Day 1 
Day 1 
Day 1 of 
Every Other 
Cycle 
End of 
Treatment27 
Follow- Up26 
Visit or Assessment 
Window (days) Unless 
Otherwise Noted 
N/A 
+1 
1 
1 
1 
2 
2 
±2 days 
2 
±7 
Informed consent2 
X 
Tumor history 
X 
Medical history 
X 
Physical examination 
X 
(X) 
(X) 
X 
X 
X 
Baseline signs and 
symptoms3 
X 
X 
Height 
X 
Weight 
X 
X 
X 
X 
X 
Vital signs4 
X 
X 
X 
X 
X 
X 
X 
Performance status5 
X 
X 
X 
X 
X 
X 
Contraceptive check (as 
appropriate) 
(X) 
X 
X 
X 
X 
Laboratory 
Hematology6 
X 
(X) 
X 
X 
X 
X 
X 
Blood Chemistry7 
X 
(X) 
X 
X 
X 
X 
X 
Lipids8 
X 
(X) 
X 
X 
X 
X 
X 
Hypogonadism (male 
patients)9 
X 
X 
X 
C5D1 and Q 
4 cycles thereafter 
Every 4 Cycles 
X 
Coagulation10 
X 
(X) 
X 
Urinalysis11 
X 
(X) 
X 
Pregnancy test12 
X 
X 
(X) 
X 
X 
X 
X 
(12 lead) ECG13 
X 
X 
X 
X 
X 
X 
X 
(upto Cycle 5) 
X 

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CYCLE 1 
(21 days) 
CYCLE 2 
(21 days) 
CYCLES 3 – 
38 (Up to Month 
30) 
(21 days) 
CYCLES 
>38 (Months 
>30) 
(21 days) 
Protocol Activity 
Screen1 
(28 days) 
Lead-in 
PK 
(Day -7) 
Day 1 Day 8 
Day 15 
Day 1 
Day 1 
Day 1 of 
Every Other 
Cycle 
End of 
Treatment27 
Follow- Up26 
Visit or Assessment 
Window (days) Unless 
Otherwise Noted 
N/A 
+1 
1 
1 
1 
2 
2 
±2 days 
2 
±7 
LVEF Assessments 
(Echocardiogram or 
MUGA)28 
X 
X 
X 
Every 4 Cycles 
X 
For France and Germany 
only: Transthoracic 
echocardiogram to assess 
PAP and right heart 
function32 
Every 6 months 
±2 weeks 
Every 
6 months 
±2 weeks 
X 
Registration and Treatment 
Registration14 
X 
(X) 
PF-06463922 Treatment15,16 
X 
Once a day continuously 
Tumor Assessments 
CT and MRI Scan or 
Equivalent17 
X 
X and then every 
6 weeks 1 week 
Every 
12 weeks ±1 
(X) 
(X) 
Cerebrospinal fluid if 
leptomenigeal/carcinomatous 
meningitis [LM/CM]disease 
is present18 
X 
Other Clinical Assessments 
Adverse Events19 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant medications and 
non drug supportive 
interventions20 
X 
X 
X 
X 
X 
X 
EORTC QLQ-C30, 
QLQ-LC1325 
X 
X 
X 
X 
X 
X 

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CYCLE 1 
(21 days) 
CYCLE 2 
(21 days) 
CYCLES 3 – 
38 (Up to Month 
30) 
(21 days) 
CYCLES 
>38 (Months 
>30) 
(21 days) 
Protocol Activity 
Screen1 
(28 days) 
Lead-in 
PK 
(Day -7) 
Day 1 Day 8 
Day 15 
Day 1 
Day 1 
Day 1 of 
Every Other 
Cycle 
End of 
Treatment27 
Follow- Up26 
Visit or Assessment 
Window (days) Unless 
Otherwise Noted 
N/A 
+1 
1 
1 
1 
2 
2 
±2 days 
2 
±7 
Cognitive Assessment29 
X 
X 
X 
X 
X up to Cycle 
6 and then D1 of 
every other cycle 
X 
X 
Mood Assessment30 
X 
X 
X 
X up to Cycle 
6 and then D1 of 
every other cycle 
X 
X 
Suicidal Ideation and 
Behavior31 
X 
X 
X 
X up to Cycle 
6 and then D1 of 
every other cycle 
X 
X 
Survival Follow-up 
X 
Other Samples 
Archival Tumor Tissue 
Specimen21 
X 
De Novo Tumor Specimens22 
X 
‘X’ 
Blood Specimens for 
Circulating Nucleic Acid 
(CNA) Profiling23 
X 
X 
X 
Banked Biospecimen24 
X 
Footnotes (X) refer to specific footnote when the measurement may be optional /repeat measurement might not be required. For example, if a patient 
will not have the Lead-In (Day -7) Visit, some assessments may be required on Cycle 1 Day 1 instead of Day -7 and vise versa. 
 
1. 
Screening: To be obtained within 28 days prior to registration. 
2. 
Informed Consent: Must be obtained prior to undergoing any study-specific procedures that are not considered standard of care. 
3. 
Baseline Signs & Symptoms: Patients will be asked about any signs and symptoms experienced within the 14 days prior to study entry. Worsening Baseline signs and 
symptoms will be recorded on the Adverse Events CRF page. 
4. 
Vital signs: blood pressure and pulse rate to be recorded in sitting position. 
5. 
Performance Status: use ECOG – see Appendix 4. 

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6. 
Hematology: No need to repeat on C1D1 if baseline assessment performed within 7 days prior to that date. See Assessments section for Laboratory Tests in Appendix 2. For 
those visits after C1D1, hematology labs may be done within 72 hours of dosing with results checked prior to dosing. 
7. 
Blood Chemistry: No need to repeat on C1D1 if baseline assessment performed within 7 days prior to that date. See Assessments section for Laboratory Tests in 
Appendix 2. For those visits after C1D1, blood chemistry may be done within 72 hours of dosing with results checked prior to dosing. 
8. 
Lipids: No need to repeat on C1D1 if baseline assessment performed within 7 days prior to that date. See Assessments section for Laboratory Tests in Appendix 2. For those 
visits after C1D1, lipids may be done within 72 hours of dosing with results checked prior to dosing. 
9. 
Hypogonadism Laboratory Test: to be performed in male patients only. The required blood tests are reported in Appendix 2. Blood draws MUST be done between 
08.00-11.00 AM. Should a decrease of 25% from baseline be observed in total testosterone or free testosterone a repeat laboroatory analysis of both these parameters must 
be performed at the next clinical visit to confirm hypogonadism. 
10. Coagulation: No need to repeat on C1D1 if baseline assessment performed within 7 days prior to that date. See Assessments section for Laboratory Tests in Appendix 2. 
For those visits after C1D1, coagulation may be done within 72 hours of dosing with results checked prior to dosing. 
11. Urinalysis: Dipstick is acceptable. Microscopic analyses if dipstick abnormal. No need to repeat on C1D1 if baseline assessment performed within 7 days prior to that date. 
See Assessments section for Laboratory Tests in Appendix 2. For those visits after C1D1, urinalysis may be done within 72 hours of dosing with results checked prior to 
dosing. 
12. Serum Pregnancy Test: For female patients of childbearing potential, a serum or urine pregnancy test, with sensitivity of at least 25 mIU/mL, will be performed on two 
occasions prior to starting study therapy - once at the start of screening and once at the baseline visit, immediately before investigational product administration. Pregnancy 
tests will also be routinely repeated at every cycle during the active treatment period (every other cycle beyond 30 months), at the end of study therapy and additionally 
whenever one menstrual cycle is missed or when potential pregnancy is otherwise suspected. Additional pregnancy tests may also be undertaken if requested by IRB/IECs or 
if required by local regulations. 
13. Triplicate 12-lead ECGs: At each time point, 3 consecutive 12-lead ECGs will be performed approximately 2 minutes apart to determine mean QTc interval. ECGs will be 
collected as follows: a) at Screening, b) Day -7 (Lead-in) at pre-dose, 1 hr, 2 hr and 4 hrs post-dose, c) Cycle 1 Day 1, Day 8, and Day 15 at pre-dose, 1 hr and 2 hrs post-dose, 
d) Cycles 2-5 Day 1 at pre-dose and 1 hr and 2 hrs post-dose and e) End of Treatment. If at any of these time-points the mean QTc is prolonged (501 msec), the ECGs 
should be re-evaluated by a qualified person at the institution for confirmation. Additional triplicate ECGs may be performed as clinically indicated. 
When an ECG and PK sample are scheduled at the same time, ECG assessments should be performed prior to PK sample such that the PK sample is collected at the nominal 
time (but regardless, the exact time of ECG assessment and PK collection should always be recorded). 
14. Registration: Registration will be within 2 days prior to lead-in or study treatment start. 
15. Trial Treatment: described in the Study Treatments section. 
16. Lead-in PF-06463922 Dose: A single dose of PF-06463922 will be given on Day –7 (lead-in period) for 10 Non-Japanese and 3 Japanese (non-LIC) patients, after which 
exemptions to this lead- in period requirement may be granted after discussion with Sponsor. Consideration will be given by the sponsor to shorten the duration of the lead in 
period for those patients who experience disease related symptom flare. 

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17. Tumor Assessment: Tumor assessments will include all known or suspected disease sites. CT or MRI scans of Chest Abdomin Pelvis [CAP] and MRI of the brain will be 
performed at screening. Gadolinium contrast enhanced MRI must be used for assessment of CNS lesions with contingent slices of 1 mm for lesions 5 mm – 10 mm in size, 
5mm for lesions greater than 10mm. Bone scans (or bone MRI if preferred by investigator) will be performed at baseline for all patients and repeated every 12 weeks on 
study only if evidence of bone metastases is observed at baseline. For all tumor assessments, the method of assessment that was used at baseline should be the same method 
used throughout the study. CT and MRI scans to be done at every 6 weeks 1 week up to approximately 30 months, and then every 12 weeks ±1 week beyond 30 monthsand 
responses will be confirmed 4 weeks later (RECIST v1.1) until documented progression of disease. For patients with bone involvement at Screening, CT or MRI or other 
appropriate imaging for bone assessment will be done every 6 weeks 1 week up to approximately 30 months, and then every 12 weeks ±1 week beyond 30 months (in 
addition to the every 12 week bone scan or bone MRI for detection of new disease) and responses will be confirmed 4 weeks later (RECIST v1.1) until documented 
progression of disease. For patients who have documented disease progression but are still receiving PF-06463922, CT and MRI scans are to be done according to local 
institutional standard of care. Every effort should be made to maintain the assessment scheduling relative to Cycle 1 Day 1 especially if there are dosing cycle interruptions 
due to toxicities. Tumor assessment should be repeated at the end of treatment and study visits if more than 6 weeks (more than 12 weeks beyond 30 months) have passed 
since the last evaluation. Tumor assessments will continue until progression of disease or a new anti-cancer therapy has commenced. For all patients, copies of radiologic 
images must be available for independent central radiology review as determined by the sponsor. Detailed instructions will be provided in the Study Reference Manual. 
18. Diagnostic Cerebrospinal fluid (CSF) CSF analysis will not be required unless patients have suspected or confirmed leptomeningeal carcinomatosis not visualised on MRI. 
When applicable, CSF sample will be collected at Screening (optional CSF collection post Screening). See PK assessments for PF-06463922 CSF concentration sampling 
(optional). 
19. Adverse Event (AE) Assessments: Adverse events should be documented and recorded at each visit using NCI CTCAE version 4.03. Patients must be followed for AEs for 
28 days after the last treatment administration or until all drug related toxicities have resolved, whichever is later; or earlier than 28 days should the patient commence another 
anti-cancer therapy in the meantime. For SAEs, the active reporting period to Pfizer or its designated representative begins from the time that the patient provides informed 
consent, which is obtained prior to the patient’s participation in the study, ie, prior to undergoing any study-related procedure and/or receiving investigational product, through 
and including 28 calendar days after the last administration of the investigational product. Serious adverse events occurring to a patient after the active reporting period has 
ended should be reported to the Sponsor if the investigator becomes aware of them; at a minimum, all serious adverse events that the investigator believes have at least a 
reasonable possibility of being related to study drug are to be reported to the Sponsor. 
20. Concomitant Medications and Non-Drug Supportive Interventions: All concomitant medications and non-drug supportive interventions should be recorded in the CRF. 
21. Archival Tumor Tissue Specimens: All patients will provide a formalin-fixed paraffin embedded (FFPE) archival tumor specimen, specifically a FFPE tissue block that 
contain sufficient tissue to generate at least 6 (preferably 12) unstained slides, each with tissue sections that are 5 microns thick, or at least 6 (preferably 12) unbaked glass 
slides, each containing an unstained 5 micron FFPE tissue section if FFPE tissue block cannot be submitted. Specimens will be sent to the Sponsor-designated central 
laboratories for assessment of biomarkers potentially associated with sensitivity and/or resistance to PF-06463922 (eg, ALK mutations, mutations/copy number variation of 
candidate genes, expression and/or phosphorylation of candidate proteins, etc); for ROS1+ NSCLC patients specimens will be sent to the Sponsor-designated central 
laboratory for ROS1 status confirmation. 
22. De Novo Tumor Specimens: De novo tumor core biopsy collection will be mandatory at screening unless it is considered to pose a safety risk to the patient, in the opinion of 
the Investigator, and only after discussion with the Sponsor; please refer to Section 7.3 for further guidance. For patients who are treatment naïve at Screening (ie, no 
previous systemic therapy in the metastatic setting), a de novo tumor biopsy is not required if a previous tumor biopsy was performed within 4 months of first dose of 
PF-06463922. Pleural effusions (PE) cell pellets may substitute for tumor core biopsy as appropriate. Fine needle aspiration (FNA) samples (2-3 pathes prepared as FFPE 
cell block) are not preferred and should only be performed in the event a biopsy or pleural effusion cell pellet is not safe or feasible. If local country regulations do not allow 
for tissue block to be submitted, 5-micron FFPE tumor tissue slides (at least 12 slides) are acceptable. Specimens will be sent to the Sponsor-designated central laboratories 
for assessment of biomarkers potentially associated with sensitivity and/or resistance to PF-06463922 (eg, ALK mutations, mutations/copy number variation of candidate 
genes, expression and/or phosphorylation of candidate proteins, etc); for ROS1+ NSCLC patients specimens will be sent to the Sponsor-designated central laboratory for 
ROS1 status confirmation. In addition, optional de novo tumor biospy collection at the time of progression is encouraged. Tumor tissue specimens from all patients will be 
used for additional biomarker analyses. Details for handling of these samples including processing, storage, and shipment will be provided in the Study Manual. 

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23. Blood Specimens for Circulating Nucleic Acid (CNA) Profiling: 10 mL blood specimen optimized for plasma preparation for nucleic acid analysis (eg, circulating free 
DNA (cfDNA) or RNA (cfRNA)) will be collected at screening, at the end of Cycle 2 (matching the first tumor restaging, in practical terms this may be C3D1 pre-dose) and 
at End of Treatment. Details for handling of these specimens including processing, storage, and shipment will be provided in the Study Manual. 
24. Banked Biospecimens: Unless prohibited by local regulations, a blood sample (Prep D1: 4 mL K2 EDTA whole blood collection optimized for DNA analysis), retained for 
pharmacogenomic analyses, will be collected at screening. 
25. EORTC QLQ-C30 and QLQ-LC13: Patients must complete all EORTC QLQ-C30 and QLQ-LC13 self-assessment questionnaires in the clinic at the specified time points 
prior to dosing. At Day -7, or Cycle 1 Day 1 if this is the first dose, site staff (eg, site coordinators) should instruct patients that the assessment should be completed without 
help from friends or family members and also recommend that this assessment be completed in the morning. All scheduled assessments of the EORTC QLQ-C30 and QLQ 
LC13 cannot be taken home and must be completed in the clinic prior to any other study or medical procedures. 
26. Follow up: At least 28 days, and no more than 35 days after discontinuation of treatment patients will return to undergo review of concomitant medications and assessment 
for resolution of any treatment-related toxicity. Patients continuing to experience toxicity at this point following discontinuation of treatment will continue to be followed at 
least every 4 weeks until resolution or determination, in the clinical judgment of the Investigator, that no further improvement is expected. Patients discontinuating treatment 
for reasons other than progression of disease will continue to perform tumor assessments until PD or a new anti-cancer therapy is commenced. Bimonthly survival followup 
after PD or new anti-cancer therapy has commenced will be performed (telephone contact is acceptable). For patients who receive crizotinib following treatment with 
PF-06463922, follow-up is according to Appendix 11. 
27. End of Treatment Visit: Obtain these assessments if not completed in the last week (last 6 weeks for tumor assessments up to 30 months and then last 12 weeks beyond 
30 months). For patients who receive crizotinib following treatment with PF-06463922, assessments at the End of Treatment visit are according to Appendix 11. 
28. LVEF Assessments: Echocardiogram or MUGA will be performed at Screening, before dosing at Day 1 Cycle 2, before dosing at Day 1 Cycle 3, before dosing at 
Day 1 Cycle 5 and every two cycles thereafter (ie, before dosing at Day 1 Cycle 7, Day 1 Cycle 9, etc.) up to approximately 30 months, and then every 4 Cycles thereafter, 
and at the End of Treatment visit. A 2 days time window applicable at the discretion of the investigator is allowed at all time points. The same method should be used at 
each time point. 
29. Cognitive Assessment: A computerized cognitive test compromised of verbal learning, psychomotor function, attention and memory will be administered to patients prior to 
study drug dosing. This test will take approximately 10-20 minutes to complete and will be administered via qualified site personnel. A practice test will be performed at 
Screening and a baseline test will be done on the first day of PF-06463922 dosing (ie, day -7 or C1D1, whichever is their first dose), and then prior to dosing on Day 1 of 
Cycle 2 –Cycle 6 (±1 week). After C6D1, this test will be administed prior to dosing on D1 of every other cycle ±1 week (ie, C8D1, C10D1, etc.). 
30. Mood Assessment: An assessment of mood via the Beck Depression Inventory-II (BDI-II) scale will be administered to patients prior to the first day of PF-06463922 dosing 
(ie, day -7 or C1D1, whichever is their first dose) and then prior to dosing on Day 1 of Cycle 2 –Cycle 6 (±1 week). After C6D1, this test will be administered prior to dosing 
on D1 of every other cycle ±1 week (ie, C8D1, C10D1, etc.). 
31. Suicidal Ideation and Behavior Assessment: An assessment of suicidal ideation and behavior via the Columbia Suicide Severity Rating Scale (C-SSRS) will be 
administered to patients prior to study drug dosing (ie, day -7 or C1D1, whichever is their first dose) and then prior to dosing on Day 1 of Cycle 2 –Cycle 6 (±1 week). After 
C6D1, this will be administered prior to dosing on D1 of every other cycle ±1 week (ie, C8D1, C10D1, etc.). 
32. For sites in France and Germany, a transthoracic echocardiogram (TTE) will be performed every 6 months (±2 weeks) during treatment, and only at the End of Treatment visit 
if the previous assessment was >1 month. Pulmonary arterial pressure (PAP) will be assessed. 

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Table 5. 
Phase 2 Portion of the Study - Pharmacokinetic Assessments (Not Applicable for Patients in the DDI and Holter 
Study) 
Note: After cycle 10, PK samples collection is not required anymore, except for CSF sample collection as detailed on Footnotes 
4 and 5 
 
CYCLE 1 
(21 days) 
CYCLE 2-5 
(21 days) 
CYCLE 6, 8 and 10 
(21 days) 
Protocol Activity 
Screen 
(28 days) 
Lead-in 
PK 
(Day -7) 
Day 1 
Day 8 
Day 15 
Day 1 
Day 1 
Visit Window 
N/A 
+1 
1 
1 
1 
2 
2 
Full PF-06463922 PK samples1 
X 
X 
X 
X 
X 
X 
Sparse PF-06463922 PK samples2 
X 
X 
X 
PF-06463922 metabolite profiling 
blood samples3 
X 
Cerebrospinal fluid (CSF) 
PF-06463922 concentration 
(optional)4 
Any time during steady state, ideally 4-6 hrs and 8-9 hrs post-dose 
Blood sample (whenever CSF for 
PF-06463922 is collected)5 
Same time as CSF PF-06463922 concentration sample collected 
Footnotes. 
 
 
1. PF-06463922 Full PK Sampling (10 Non-Japanese patients and 3 Japanese (non-LIC) patients enrolled in the trial): NO LONGER APPLICABLE upon Amendment 
6. Blood samples will be collected for PK sampling on the following days 1). Day-7 (Lead-in) Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24, 48, 72, 96 and 120 hours post dose 
(2 samples between 48 to 120 hrs). 2) Cycle 1 Day 1 and Day 8 at pre-dose, 1 hr, 2 hr, and 4 hr post dose, 3) Cycle 1 Day 15: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hrs. 4) 
Day 1 of Cycles 2 to 5: Pre-dose 1 hr and 2 hrs post-dose 5) Day 1 of Cycle 6 and Day 1 of every other Cycle thereafter: Pre-dose. Sites will be notified via letter when full 
PK sampling is no longer required (ie, after 10 Non-Japanese patients and 3 Japanese (non-LIC) patients). Where required by local regulations and after agreement by the 
study sponsor, patients may be hospitalized for PK sampling. For all other patients, sparse plasma samples will be collected as per table footnote 2 below. Additional PK 
plasma samples may also need to be collected at the time of optional CSF sample collection according to footnote 4. 
2. Sparse Plasma Sampling for PF-06463922 (in all patients after 10 Non-Japanese and 3 Japanese (non-LIC) patients with full PK sampling) Blood samples will be 
collected pre-dose on Day 1 of Cycles 1-5 and pre-dose on Day 1 of Cycle 6,Day 1 of Cycle 8 and Day 1 of Cycle 10. Sites will be notifed via letter when sparse PK sampling 
is in effect. 

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3. PF-06463922 Metabolite profiling (10 Non-Japanese and 3 Japanese (non-LIC) patients enrolled in the trial): NO LONGER APPLICABLE upon Amendment 6. 
Blood samples will be collected at steady-state on Cycle 1 Day 15: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, and 24 hrs post-dose. Sites will be notified via letter when metabolite 
profiling is no longer required. 
4. CSF PF-06463922 Concentration Sample (Optional): If a patient undergoes a lumber puncture, a sample of CSF should be collected for exploratory analysis of 
PF-06463922 concentration, if possible. If this CSF sample is collected, a blood sample for PK analysis should also be collected at approximately the same time as the CSF 
sample. If scheduling permits, one CSF sample should be taken between 4 and 6 hours post dose. If it is possible to take a second sample, collection should be between 8 and 
9 hours post-dose. 
5. If a CSF PF-06463922concentration sample is collected, a blood sample for PK analysis should be collected at approximately the same time as the CSF sample. 

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Table 6. 
Drug-Drug Interaction and Holter Monitoring Study 
Note: The current table is no longer applicable after the approval of Amendment 8 
 
Screen 
Pre Cycle 1 
CYCLE 1 
(21 days) 
CYCLE 2 
(21 days) 
CYCLES 3 – 
38 (Up to 
Month 30) 
(21 days) 
CYCLES 
>38 
(Months ˃30) 
(21 days) 
Post Treatment 
Protocol Activity 
Screen1 
(28 day 
s) 
Lead-in 
PK 
(Day -2) 
Baseline 
ECG 
Day -1 
Day 1 Day 8 
Day 14 Day 15 
Day 1 
Day 1 
Day 1 of 
Every Other 
Cycle 
End of 
Treatment 
33 
Follow- Up34 
Visit or Assessment 
Window (days) Unless 
Otherwise Noted 
N/A 
N/A 
N/A 
1 
1 
1 
1 
2 
2 
±2 days 
2 
±7 
Informed consent2 
X 
Tumor history 
X 
Medical history 
X 
Physical examination 
X 
(X) 
(X) 
X 
X 
X 
Baseline signs and 
symptoms3 
X 
Height 
X 
Weight 
X 
X 
X 
X 
X 
Vital signs4 
X 
X 
X 
X 
X 
X 
X 
Performance status5 
X 
X 
X 
X 
X 
X 
Contraceptive check (as 
appropriate) 
X 
X 
X 
X 
Laboratory 
Hematology6 
X 
(X) 
X 
X 
X 
X 
X 
Blood Chemistry7 
X 
(X) 
X 
X 
X 
X 
X 
Lipids8 
X 
(X) 
X 
X 
X 
X 
X 
Hypogonadism (male 
patients)9 
X 
X 
X 
C5D1 and Q 
4 cycles 
thereafter 
Q 4 Cycles 
X 
Coagulation10 
X 
(X) 
X 
Urinalysis11 
X 
(X) 
X 
Pregnancy test12 
X 
X 
X 
X 
X 
X 

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Screen 
Pre Cycle 1 
CYCLE 1 
(21 days) 
CYCLE 2 
(21 days) 
CYCLES 3 – 
38 (Up to 
Month 30) 
(21 days) 
CYCLES 
>38 
(Months ˃30) 
(21 days) 
Post Treatment 
Protocol Activity 
Screen1 
(28 day 
s) 
Lead-in 
PK 
(Day -2) 
Baseline 
ECG 
Day -1 
Day 1 Day 8 
Day 14 Day 15 
Day 1 
Day 1 
Day 1 of 
Every Other 
Cycle 
End of 
Treatment
33 
Follow- Up34 
Visit or Assessment 
Window (days) Unless 
Otherwise Noted 
N/A 
N/A 
N/A 
1 
1 
1 
1 
2 
2 
±2 days 
2 
±7 
(12 lead) ECG13 
X 
X 
X 
(up to Cycle 5) 
X 
LVEF Assessments 
(Echocardiogram or 
MUGA)35 
X 
X 
X 
Q 4 Cycles 
X 
Registration and 
Treatment 
Registration14 
X 
PF-06463922 Treatment15 
Once a day continuously 
PK and Holter 
Serial blood samples for 
PF-06463922 PK16 
X 
X 
X 
X (Cycles 4, 6, 
8 and 10) 
Blood samples for 
PF-06463922 metabolite(s)17 
X 
X 
Single-dose of probe18 
X 
X 
Serial blood plasma 
samples for 
probe substrate PK18 
X 
X 
Pharmacogenomics 
Sample19 
X 
24-Hour Continuous 
ECG20 
X 
X 
X 
Tumor Assessments 
CT and MRI Scan or 
Equivalent21 
X 
X and then 
every 6 weeks 
1 week 
Every 
12 weeks ±1 
(X) 
(X) 

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Screen 
Pre Cycle 1 
CYCLE 1 
(21 days) 
CYCLE 2 
(21 days) 
CYCLES 3 – 
38 (Up to 
Month 30) 
(21 days) 
CYCLES 
>38 
(Months ˃30) 
(21 days) 
Post Treatment 
Protocol Activity 
Screen1 
(28 day 
s) 
Lead-in 
PK 
(Day -2) 
Baseline 
ECG 
Day -1 
Day 1 Day 8 
Day 14 Day 15 
Day 1 
Day 1 
Day 1 of 
Every Other 
Cycle 
End of 
Treatment
33 
Follow- Up34 
Visit or Assessment 
Window (days) Unless 
Otherwise Noted 
N/A 
N/A 
N/A 
1 
1 
1 
1 
2 
2 
±2 days 
2 
±7 
Cerebrospinal fluid if 
leptomenigeal/carcinomat 
ous meningitis 
[LM/CM]disease is 
present22 
X 
Optional and as clinically indicated 
Other Clinical 
Assessments 
Adverse Events23 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant medications 
and non drug supportive 
interventions24 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
EORTC QLQ-C30, 
QLQ-LC1325 
X 
X 
X 
X 
X 
Cognitive Assessment26 
X 
X 
X 
X up to 
Cycle 6 and 
then D1 of 
every other 
cycle 
X 
X 
Mood Assessment27 
X 
X 
X up to 
Cycle 6 and 
then D1 of 
every other 
cycle 
X 
X 

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Screen 
Pre Cycle 1 
CYCLE 1 
(21 days) 
CYCLE 2 
(21 days) 
CYCLES 3 – 
38 (Up to 
Month 30) 
(21 days) 
CYCLES 
>38 
(Months ˃30) 
(21 days) 
Post Treatment 
Protocol Activity 
Screen1 
(28 day 
s) 
Lead-in 
PK 
(Day -2) 
Baseline 
ECG 
Day -1 
Day 1 Day 8 
Day 14 Day 15 
Day 1 
Day 1 
Day 1 of 
Every Other 
Cycle 
End of 
Treatment
33 
Follow- Up34 
Visit or Assessment 
Window (days) Unless 
Otherwise Noted 
N/A 
N/A 
N/A 
1 
1 
1 
1 
2 
2 
±2 days 
2 
±7 
Suicidal Ideation and 
Behavior28 
X 
X 
X up to 
Cycle 6 and 
then D1 of 
every other 
cycle 
X 
X 
Survival Follow-up 
X 
Other Samples 
Archival Tumor Tissue 
Specimen29 
X 
De Novo Tumor 
Specimens30 
X 
‘X’ 
Blood Specimens for 
Circulating Nucleic Acid 
(CNA) Profiling31 
X 
X 
X 
Banked Biospecimen32 
X 
Cerebrospinal fluid (CSF) 
PF-06463922 
concentration (optional)36 
Any time during steady state, ideally 
4-6 hrs and 8-9 hrs post-dose 
Blood sample (whenever 
CSF for PF-06463922 is 
collected)37 
Same time as CSF 
PF-06463922 concentration sample 
collected 
Footnotes (X) refer to specific footnote when the measurement may be optional /repeat measurement might not be required. 
 
1. 
Screening: To be obtained within 28 days prior to registration. 
2. 
Informed Consent: Must be obtained prior to undergoing any study-specific procedures that are not considered standard of care. 
3. 
Baseline Signs & Symptoms: Patients will be asked about any signs and symptoms experienced within the 14 days prior to study entry. Worsening Baseline signs and 
symptoms will be recorded on the Adverse Events CRF page. 

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4. 
Vital signs: blood pressure and pulse rate to be recorded in sitting position. 
5. 
Performance Status: use ECOG – see Appendix 4. 
6. 
Hematology: No need to repeat on C1D1 if baseline assessment performed within 7 days prior to that date. See Assessments section for Laboratory Tests in Appendix 2. For 
those visits after C1D1, hematology labs may be done within 72 hours of dosing with results checked prior to dosing. 
7. 
Blood Chemistry: No need to repeat on C1D1 if baseline assessment performed within 7 days prior to that date. See Assessments section for Laboratory Tests in 
Appendix 2. For those visits after C1D1, blood chemistry may be done within 72 hours of dosing with results checked prior to dosing. 
8. 
Lipids: No need to repeat on C1D1 if baseline assessment performed within 7 days prior to that date. See Assessments section for Laboratory Tests in Appendix 2. For those 
visits after C1D1, lipids may be done within 72 hours of dosing with results checked prior to dosing. 
9. 
Hypogonadism Laboratory Test: to be performed in male patients only. The required blood tests are reported in Appendix 2. Blood draws MUST be done between 
08.00-11.00 AM. Should a decrease of 25% from baseline be observed in total testosterone or free testosterone a repeat laboroatory analysis of both these parameters must 
be performed at the next clinical visit to confirm hypogonadism. 
10. Coagulation: No need to repeat on C1D1 if baseline assessment performed within 7 days prior to that date. See Assessments section for Laboratory Tests in Appendix 2. 
For those visits after C1D1, coagulation may be done within 72 hours of dosing with results checked prior to dosing. 
11. Urinalysis: Dipstick is acceptable. Microscopic analyses if dipstick abnormal. No need to repeat on C1D1 if baseline assessment performed within 7 days prior to that date. 
See Assessments section for Laboratory Tests in Appendix 2. For those visits after C1D1, urinalysis may be done within 72 hours of dosing with results checked prior to 
dosing. 
12. Serum Pregnancy Test: For female patients of childbearing potential, a serum or urine pregnancy test, with sensitivity of at least 25 mIU/mL, will be performed on two 
occasions prior to starting study therapy - once at the start of screening and once at the baseline visit, immediately before investigational product administration. Pregnancy 
tests will also be routinely repeated at every cycle during the active treatment period (every other cycle beyond 30 months), at the end of study therapy and additionally 
whenever one menstrual cycle is missed or when potential pregnancy is otherwise suspected. Additional pregnancy tests may also be undertaken if requested by IRB/IECs or 
if required by local regulations. 
13. Triplicate 12-lead ECGs: At each time point, 3 consecutive 12-lead ECGs will be performed approximately 2 minutes apart to determine mean QTc interval. ECGs will be 
collected as follows: a) at Screening, b) Cycles 2-5 Day 1 at pre-dose and 1 hr and 2 hrs post-dose and e) End of Treatment. If at any of these time-points the mean QTc is 
prolonged (501 msec), the ECGs should be re-evaluated by a qualified person at the institution for confirmation. Additional triplicate ECGs may be performed as clinically 
indicated. 
When an ECG and PK sample are scheduled at the same time, ECG assessments should be performed prior to PK sample such that the PK sample is collected at the nominal 
time (but regardless, the exact time of ECG assessment and PK collection should always be recorded). 
14. Registration: Registration will be within 2 days prior to lead-in. 
15. Trial Treatment: described in the Study Treatments section. 
16. PF 06463922 Full PK Sampling: Blood samples (4 mL each) will be collected for PK sampling on the following days: 1). Cycle 1 Day 1 and Cycle 1 Day 15: Pre dose, 0.5, 
1, 2, 3, 4, 6, 8, , and 24 hrs post PF-06463922 dose. 2) Day 1 of Cycle 2, Cycle 4, Cycle 6, Cycle 8 and Cycle 10: Pre-dose. Where required by local regulations and after 
agreement by the study sponsor, patients may be hospitalized for PK sampling. 
17. PF 06463922 Metabolite Sample: Blood samples for evaluation of metabolite(s) will be collected in all patients in this cohort. Blood samples (4 mL each) will be collected 
on Cycle I Day 1 and at steady-state on Cycle 1 Day 15 at: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, and 24 hrs post-PF-06463922 dose (the following day). 

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18. Probe Substrate and PK for Probe Substrate: For evaluation of drug-drug interaction, eligible patients will be dosed with the probe substrate in the fasted state, when 
possible, (no food 2 hours before through 2 hours after probe substrate dosing) in the Lead-In portion on Day -2 and in combination with steady-state PF-06463922 on 
Cycle 1 Day 15. PK Sampling for probe substrates: Plasma blood samples (3ml) will be collected for PK sampling on the following days and times: 
a. 
Day-2 (Lead-in) Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, and 24 hrs post dose. 
b. 
Cycle 1 Day 15: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, and 24 hrs post dose. 
19. Pharmacogenomic Sample: A single 4-mL blood sample will be collected at any time on Day -2 for pharmacogenomics analysis. 
20. ECG Holter Monitoring: The 24-hour continuous ECG monitoring by Holter telemetry will be in addition to the single/triplicate ECGs described in Footnote 13. Twenty 
four (24) hr continuous ECG monitoring will occur on Day -1 through Cycle 1 Day 1 and again on Cycle 1 Day 14. On Day -1, the 24-hour Holter monitoring will begin 
approximately 24 hours after probe substrate administration on Day -2. On Cycle 1 Day 14, 24-hour Holter monitoring will begin immediately prior to 
PF-06463922 administration. Additional ECG time points may be included based on emerging data. Baseline values are defined as ECG collection prior to the very first dose 
of PF-06463922. When possible, on Day-1 and Day 1 and Day 14 of Cycle 1, breakfast should be consumed at least 2 hours after the PF-06463922 dosing. When possible, 
lunch and dinner should be consumed approximately 5 and 9 hours, respectively after PF-06463922 dosing. Similarly, every attempt should be made to have the starting 
clock time for continuous Holter telemetry on Day -1 of lead-in and Days 1 and 14 of Cycle 1 be as close as possible (ie, approximately at the same clock-time). Holter ECG 
monitoring: Subjects should be supine for at least 15 minutes prior to the corresponding clock time for each scheduled PK collection time point on Day 1 and Day 14: subjects 
will remain supine for 10 minutes after which ECGs will be extracted in the following 5 minutes, followed by PK collection. ECGs on Day 1 and Day 14 will be 
time-matched for PK collection on those days. In addition, baseline ECGs will be extracted on Day -1 that are approximately time-matched with ECGs on Day 1 and Day 14. 
21. Tumor Assessment: Tumor assessments will include all known or suspected disease sites. CT or MRI scans of Chest Abdomin Pelvis [CAP] and MRI of the brain will be 
performed at screening. Gadolinium contrast enhanced MRI for must be used for assessment of CNS lesions with contingent slices of 1 mm for lesions 5 mm – 10 mm in 
size, 5mm for lesions greater than 10mm. Bone scans (or bone MRI if preferred by investigator) will be performed at baseline for all patients and repeated every 12 weeks on 
study only if evidence of bone metastases is observed at baseline. For all tumor assessments, the method of assessment that was used at baseline should be the same method 
used throughout the study. CT and MRI scans to be done at every 6 weeks 1 week up to approximately 30 months, and then every 12 weeks ±1 week beyond 30 months, 
and responses will be confirmed 4 weeks later (RECIST v1.1) until documented progression of disease. For patients with bone involvement at Screening, CT or MRI or 
other appropriate imaging for bone assessment will be done every 6 weeks 1 week up to approximately 30 months, and then every 12 weeks ±1 week beyond 30 months (in 
addition to the every 12 week bone scan or bone MRI for detection of new disease), and responses will be confirmed 4 weeks later (RECIST v1.1) until documented 
progression of disease. For patients who have documented disease progression but are still receiving PF-06463922, CT and MRI scans are to be done according to local 
institutional standard of care. Every effort should be made to maintain the assessment scheduling relative to Cycle 1 Day 1 especially if there are dosing cycle interruptions 
due to toxicities. Tumor assessment should be repeated at the end of treatment and study visits if more than 6 weeks (more than 12 weeks beyond 30 months) have passed 
since the last evaluation. Tumor assessments will continue until progression of disease or a new anti-cancer therapy has commenced. For all patients, copies of radiologic 
images must be available for independent central radiology review as determined by the sponsor. Detailed instructions will be provided in the Study Reference Manual. 
22. Diagnostic Cerebrospinal fluid (CSF) CSF analysis will not be required unless patients have suspected or confirmed leptomeningeal carcinomatosis not visualised on MRI. 
When applicable, CSF sample will be collected at Screening (optional CSF collection post Screening). See PK assessments for PF-06463922 CSF concentration sampling 
(optional). 
23. Adverse Event (AE) Assessments: Adverse events should be documented and recorded at each visit using NCI CTCAE version 4.03. Patients must be followed for AEs for 
28 days after the last treatment administration or until all drug related toxicities have resolved, whichever is later; or earlier than 28 days should the patient commence another 
anti-cancer therapy in the meantime. For SAEs, the active reporting period to Pfizer or its designated representative begins from the time that the patient provides informed 
consent, which is obtained prior to the patient’s participation in the study, ie, prior to undergoing any study-related procedure and/or receiving investigational product, through 
and including 28 calendar days after the last administration of the investigational product. Serious adverse events occurring to a patient after the active reporting period has 
ended should be reported to the Sponsor if the investigator becomes aware of them; at a minimum, all serious adverse events that the investigator believes have at least a 
reasonable possibility of being related to study drug are to be reported to the Sponsor. 

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24. Concomitant Medications and Non-Drug Supportive Interventions: All concomitant medications and non-drug supportive interventions should be recorded in the CRF. 
25. EORTC QLQ C30 and QLQ LC13: Patients must complete all EORTC QLQ C30 and QLQ LC13 self assessment questionnaires in the clinic at the specified time points 
prior to dosing. On Cycle 1 Day 1, site staff (eg, site coordinators) should instruct patients that the assessment should be completed without help from friends or family 
members and also recommend that this assessment be completed in the morning. All scheduled assessments of the EORTC QLQ C30 and QLQ LC13 cannot be taken home 
and must be completed in the clinic prior to any other study or medical procedures. 
26. Cognitive Assessment: A computerized cognitive test compromised of verbal learning, psychomotor function, attention and memory will be administered to patients prior to 
study drug dosing. This test will take approximately 10-20 minutes to complete and will be administered via qualified site personnel. A practice test will be performed at 
Screening and a baseline test will be done on the first day of PF-06463922 dosing (ie, C1D1), and then prior to dosing on Day 1 of Cycle 2 - Cycle 6 (±1 week). After C6D1, 
this test will be administed prior to dosing on D1 of every other cycle ±1 week (ie, C8D1, C10D1, etc.). 
27. Mood Assessment: An assessment of mood via the Beck Depression Inventory-II (BDI-II) scale will be administered to patients prior to the first day of PF-06463922 dosing 
(ie, C1D1) and then prior to dosing on Day 1 of Cycle 2 –Cycle 6 (±1 week). After C6D1, this test will be administered prior to dosing on D1 of every other cycle ±1 week 
(ie, C8D1, C10D1, etc.). 
28. Suicidal Ideation and Behavior Assessment: An assessment of suicidal ideation and behavior via the Columbia Suicide Severity Rating Scale (C-SSRS) will be 
administered to patients prior to study drug dosing (ie, C1D1), and then prior to dosing on Day 1 of Cycle 2 –Cycle 6 (±1 week). After C6D1, this will be administered prior 
to dosing on D1 of every other cycle ±1 week (ie, C8D1, C10D1, etc.). 
29. Archival Tumor Tissue Specimens: All patients will provide a formalin fixed paraffin embedded (FFPE) archival tumor specimen, specifically a FFPE tissue block that 
contain sufficient tissue to generate at least 6 (preferably 12) unstained slides, each with tissue sections that are 5 microns thick, or at least 6 (preferably 12) unbaked glass 
slides, each containing an unstained 5 micron FFPE tissue section if FFPE tissue block cannot be submitted. Specimens will be sent to the Sponsor designated central 
laboratories for assessment of biomarkers potentially associated with sensitivity and/or resistance to PF 06463922 (eg, ALK mutations, mutations/copy number variation of 
candidate genes, expression and/or phosphorylation of candidate proteins, etc); for ROS1+ NSCLC patients specimens will be sent to the Sponsor designated central 
laboratory for ROS1 status confirmation. 
30. De Novo Tumor Specimens: De novo tumor core biopsy collection will be mandatory at screening unless it is considered to pose a safety risk to the patient, in the opinion of 
the Investigator, and only after discussion with the Sponsor; please refer to Section 7.3 for further guidance. For patients who are treatment naïve at Screening (ie, no 
previous systemic therapy in the metastatic setting), a de novo tumor biopsy is not required if a previous tumor biopsy was performed within 4 months of first dose of 
PF-06463922. Pleural effusions (PE) cell pellets may substitute for tumor core biopsy as appropriate. Fine needle aspiration (FNA) samples are not preferred and should only 
be performed in the event a biopsy or pleural effusion cell pellet is not safe or feasible. If local country regulations do not allow for core biopsy block to be submitted, 
5-micron FFPE tumor tissue slides (at least 12 slides) are acceptable. Specimens will be sent to the Sponsor-designated central laboratories for assessment of biomarkers 
potentially associated with sensitivity and/or resistance to PF-06463922 (eg, ALK mutations, mutations/copy number variation of candidate genes, expression and/or 
phosphorylation of candidate proteins, etc); for ROS1+ NSCLC patients specimens will be sent to the Sponsor-designated central laboratory for ROS1 status confirmation. In 
addition, optional de novo tumor biospy collection at the time of progression is encouraged. Tumor tissue specimens from all patients will be used for additional biomarker 
analyses. Details for handling of these samples including processing, storage, and shipment will be provided in the Study Manual. 
31. Blood Specimens for Circulating Nucleic Acid (CNA) Profiling: 10 mL blood specimen optimized for plasma preparation for nucleic acid analysis (eg, circulating free 
DNA (cfDNA) or RNA (cfRNA)) will be collected at screening, at the end of Cycle 2 (matching the first tumor restaging, in practical terms this may be C3D1 pre-dose) and 
at End of Treatment. Details for handling of these specimens including processing, storage, and shipment will be provided in the Study Manual. 
32. Banked Biospecimens: Unless prohibited by local regulations, a blood sample (Prep D1: 4 mL K2 EDTA whole blood collection optimized for DNA analysis), retained for 
pharmacogenomic analyses, will be collected at screening. 
33. End of Treatment Visit: Obtain these assessments if not completed in the last week (last 6 weeks for tumor assessments up to 30 months and then last 12 weeks beyond 
30 months). For patients who receive crizotinib following treatment with PF-06463922, assessments at the End of Treatment visit are according to Appendix 11. 

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34. Follow up: At least 28 days, and no more than 35 days after discontinuation of treatment patients will return to undergo review of concomitant medications and assessment 
for resolution of any treatment-related toxicity. Patients continuing to experience toxicity at this point following discontinuation of treatment will continue to be followed at 
least every 4 weeks until resolution or determination, in the clinical judgment of the Investigator, that no further improvement is expected. Patients discontinuating treatment 
for reasons other than progression of disease will continue to perform tumor assessments until PD or a new anti-cancer therapy is commenced. Bimonthly survival followup 
after PD or new anti-cancer therapy has commenced will be performed (telephone contact is acceptable). For patients who receive crizotinib following treatment with 
PF-06463922, follow-up is according to Appendix 11. 
35. LVEF Assessments: Echocardiogram or MUGA will be performed at Screening, before dosing at Day 1 Cycle 2, before dosing at Day 1 Cycle 3, before dosing at 
Day 1 Cycle 5 and every two cycles thereafter (ie, before dosing at Day 1 Cycle 7, Day 1 Cycle 9, etc.) up to approximately 30 months, and then every 4 Cycles thereafter, 
and at the End of Treatment visit. A 2 days time window applicable at the discretion of the investigator is allowed at all time points. The same method should be used at 
each time point. 
36. CSF PF-06463922 Concentration Sample (Optional): If a patient undergoes a lumber puncture, a sample of CSF should be collected for exploratory analysis of PF 
06463922 concentration, if possible. If this CSF sample is collected, a blood sample for PK analysis should also be collected at approximately the same time as the CSF 
sample. If scheduling permits, one CSF sample should be taken between 4 and 6 hours post dose. If it is possible to take a second sample, collection should be between 8 and 
9 hours post-dose. 
37. Blood PK for Optional CSF sample: If a CSF PF-06463922 concentration sample is collected, a blood sample for PK analysis should be collected at approximately the 
same time as the CSF sample. 

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TABLE OF CONTENTS 
LIST OF TABLES ................................................................................................................... 57 
LIST OF FIGURES .................................................................................................................. 58 
APPENDICES .......................................................................................................................... 58 
1. INTRODUCTION ................................................................................................................ 60 
1.1. Indication ................................................................................................................. 60 
1.2. Background .............................................................................................................. 60 
1.2.1. Efficacy of Targeted Inhibitors in Patients with ALK+ 
[rearrangement (WT) and resistance mutations (mu)] and ROS1+ 
NSCLC ............................................................................................................. 60 
1.3. PF-06463922............................................................................................................ 61 
1.3.1. PF-06463922 Background .......................................................................... 61 
1.3.2. PF-06463922 Pre-Clinical Safety Data ....................................................... 62 
1.3.2.1. Pancreas ..................................................................................... 62 
1.3.2.2. Liver .......................................................................................... 63 
1.3.2.3. Hematopoietic ............................................................................ 63 
1.3.2.4. Cardiovascular ........................................................................... 64 
1.3.2.5. Cognition and Neurological Function ....................................... 64 
1.3.2.6. Gastrointestinal .......................................................................... 65 
1.3.2.7. Effects on the Skin ..................................................................... 65 
1.3.2.8. Effects on the Thymus ............................................................... 65 
1.3.2.9. Inflammatory Response ............................................................. 66 
1.3.2.10. Effects on Peripheral Nerves ................................................... 66 
1.3.2.11. Teratogenicity .......................................................................... 66 
1.3.3. PF-06463922 Clinical Trial Experience ..................................................... 66 
1.3.4. Benefit/Risk Assessment ............................................................................. 69 
1.3.5. Safety Considerations in the Clinical Trial ................................................. 70 
1.3.6. PF-06463922 Pharmacokinetics in Animals and Projection of 
Human Pharmacokinetics ................................................................................. 72 
1.3.6.1. PF-06463922 Pharmacokinetics in Phase 1 ............................... 73 
1.3.6.2. Study B7461001 ........................................................................ 73 
1.3.6.3. Relative Bioavailability Study B7461005 ................................. 74 
1.3.7. Rationale for Selection of the Starting Dose in Phase 1 .............................. 75 

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1.3.8. Rationale for Recommended Phase 2 Starting Dose ................................... 75 
1.3.9. Rationale for Evaluation of Midazolam (MDZ) Interaction ....................... 76 
1.3.10. Rationale for Crizotinib Treatment after PF-06463922 Resistance .......... 77 
1.3.11. Rationale for Drug-drug Interaction and Holter Monitoring..................... 77 
2. STUDY OBJECTIVES AND ENDPOINTS ....................................................................... 78 
2.1. Objectives ................................................................................................................ 78 
2.2. Endpoints [Please ensure endpoints changes remain aligned with Section 9.] ........ 80 
3. STUDY DESIGN ................................................................................................................. 82 
3.1. Study Overview ....................................................................................................... 82 
3.2. Japanese Patient Lead-In Cohort (Japan Sites Only)............................................... 88 
3.3. Drug-Drug Interaction (DDI) and Holter Monitoring Study ................................... 89 
3.4. Starting Dose ........................................................................................................... 91 
3.4.1. Phase 1 ........................................................................................................ 91 
3.4.2. Phase 2 ........................................................................................................ 91 
3.4.3. Criteria for Dose Escalation ........................................................................ 91 
3.5. DLT Definition (Phase 1) ........................................................................................ 93 
3.6. MTD Definition ....................................................................................................... 94 
3.7. Recommended Phase 2 Dose (RP2D) Definition .................................................... 94 
3.8. Midazolam DDI Study (Phase 1)............................................................................. 94 
3.9. Food Effect Study (Phase 1) .................................................................................... 95 
3.10. Drug-Drug Interaction and Holter Monitoring Study ............................................ 95 
4. PATIENT SELECTION ...................................................................................................... 96 
4.1. Inclusion Criteria ..................................................................................................... 96 
4.2. Exclusion Criteria .................................................................................................... 99 
4.3. Life Style Guidelines ............................................................................................. 103 
4.3.1. Contraception ............................................................................................ 103 
4.3.1.1. Woman of Childbearing Potential (WOCBP) .......................... 104 
4.3.1.2. Contraception Methods ............................................................ 105 
4.3.2. Sunlight Exposure ..................................................................................... 105 
4.3.3. Additional Lifestyle Guidances ................................................................. 105 
4.4. Sponsor Qualified Medical Personnel .................................................................... 105 

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4.5. Mini Mental State Examination (MMSE) Rater Qualifications (Phase 1 only; 
No longer required per Amendment 6) ................................................................... 106 
4.6. Rater Requirements for Assessment of Mood and Assessment of Suicidal 
Ideation and Behavior (Phase 2 only) ..................................................................... 106 
5. STUDY TREATMENTS .................................................................................................. 106 
5.1. Allocation to Treatment ........................................................................................ 106 
5.2. Drug Supplies ....................................................................................................... 107 
5.2.1. Formulation and Packaging ..................................................................... 107 
5.2.2. Preparation and Dispensing ...................................................................... 107 
5.2.2.1. PF-06463922........................................................................... 107 
5.2.2.2. Midazolam (Phase 1 Only) ..................................................... 108 
5.2.2.3. Drug-drug Interaction and Holter Monitoring Study Probe 
Drugs............................................................................................... 108 
5.2.2.4. PF-06463922........................................................................... 108 
5.2.2.5. Midazolam (Phase 1) .............................................................. 109 
5.2.3. Food Requirements (Phase 1) .................................................................. 109 
5.2.3.1. Patients Not Included in the Food Effect Cohort ................... 109 
5.2.3.2. Requirements for the Food Effect Cohort ............................... 110 
5.2.4. Recommended Dose Modifications ......................................................... 110 
5.2.5. Dosing Interruptions ................................................................................. 111 
5.2.6. Dose Reductions ....................................................................................... 111 
5.2.7. Dose Modifications .................................................................................. 112 
5.2.8. Compliance .............................................................................................. 116 
5.2.9. Drug Storage and Drug Accountability .................................................... 116 
5.2.10. Temperature Excursions ......................................................................... 117 
5.3. Concomitant Treatments ....................................................................................... 118 
5.3.1. Concomitant Medications (Additionally, refer to Section 5.3.1.1 for 
Concomitant Medications specific to patients participating in the DDI 
and Holter Monitoring study) ....................................................................... 118 
5.3.1.1. Concomitant Medications for Patients participating in the 
DDI/Holter Monitoring Study ........................................................ 120 
5.3.2. Other Anti-Tumor or Experimental Drugs ............................................... 121 
5.3.2.1. Hematopoietic Growth Factors ............................................... 121 
5.3.2.2. Anti-Diarrheal, Anti-Emetic, and Acid-Reducing Therapy .... 121 

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5.3.2.3. Anti-Inflammatory Therapy..................................................... 122 
5.3.2.4. Cutaneous Toxicity Therapy ................................................... 122 
5.3.2.5. Testosterone Replacement ....................................................... 122 
5.3.2.6. Lipid-Lowering Therapy ......................................................... 122 
5.3.3. Supportive Care ......................................................................................... 124 
5.3.4. Surgery ...................................................................................................... 124 
6. STUDY PROCEDURES .................................................................................................... 124 
6.1. Screening ............................................................................................................... 124 
6.1.1. Archival Tumor Tissue ............................................................................. 124 
6.1.2. De Novo Tumor Biopsy ............................................................................ 125 
6.2. Study Period .......................................................................................................... 125 
6.3. Follow-up Visit ...................................................................................................... 126 
6.4. Patient Withdrawal ................................................................................................ 126 
7. ASSESSMENTS ................................................................................................................ 127 
7.1. Safety Assessment ................................................................................................. 128 
7.1.1. Pregnancy Testing ..................................................................................... 128 
7.1.2. Adverse Events ......................................................................................... 128 
7.1.3. Laboratory Safety Assessment .................................................................. 128 
7.1.4. Vital Signs and Physical Examination ...................................................... 128 
7.1.5. (12-Lead) Electrocardiograms ................................................................... 129 
7.1.6. Transthoracic echocardiogram (TTE) (France and Germany only) .......... 129 
7.1.7. Holter Monitoring (DDI and Holter Monitoring study only) ................... 130 
7.1.8. Echocardiogram and Multi Gated Acquisition Scan (MUGA) ................. 130 
7.1.9. Mini Mental State Exam (MMSE) (Phase 1 Only; no longer required 
per Amendment 6) .......................................................................................... 130 
7.1.10. Neurological Examination (Phase 1 Only) ............................................. 130 
7.1.11. Assessment of Cognitive Function (Phase 2 Only) ................................ 131 
7.1.12. Assessment of Mood (Phase 2 Only) ...................................................... 132 
7.1.13. Assessment of Suicidal Ideation and Behavior (Phase 2 Only) .............. 132 
7.2. Pharmacokinetics Assessments .............................................................................. 132 
7.2.1. Blood for PK Analysis of PF-06463922 ................................................... 132 
7.2.2. Urine for PK Analysis of PF-06463922 .................................................... 133 

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7.2.3. Blood for Metabolite Profiling of PF-06463922 ...................................... 133 
7.2.4. CSF for Analysis of PF-06463922 Concentration.................................... 134 
7.2.5. Blood for PK Analysis of Midazolam ...................................................... 134 
7.2.6. Urine Sample for 6 beta-Hydroxycortisol/Cortisol (6-OHC/C) Ratio ... 134 
7.2.7. Blood for 4 beta-Hydroxycholesterol/Cholesterol .................................... 134 
7.2.8. PK for patients participating in the Drug-Drug Interaction and Holter 
Monitoring study ........................................................................................... 134 
7.3. Pharmacodynamic Assessments ........................................................................... 135 
7.4. Tumor Response Assessments .............................................................................. 136 
7.5. Banked Biospecimens ........................................................................................... 138 
7.5.1. Markers of Drug Response ...................................................................... 138 
7.5.2. Additional Research ................................................................................. 139 
7.6. Patient-Reported Outcome Assessments .............................................................. 139 
7.6.1. EORTC QLQ-C30 and QLQ-LC13 ......................................................... 139 
8. ADVERSE EVENT REPORTING ................................................................................... 140 
8.1. Adverse Events ..................................................................................................... 140 
8.2. Reporting Period ................................................................................................... 140 
8.3. Definition of an Adverse Event ............................................................................ 141 
8.4. Medication Errors ................................................................................................. 142 
8.5. Abnormal Test Findings ....................................................................................... 142 
8.6. Serious Adverse Events ........................................................................................ 143 
8.6.1. Protocol-Specified Serious Adverse Events ............................................ 143 
8.6.2. Potential Cases of Drug-Induced Liver Injury ......................................... 143 
8.7. Hospitalization ...................................................................................................... 145 
8.8. Severity Assessment ............................................................................................. 146 
8.9. Causality Assessment ........................................................................................... 146 
8.10. Exposure During Pregnancy ............................................................................... 147 
8.11. Occupational Exposure ....................................................................................... 148 
8.12. Withdrawal Due to Adverse Events (Also See Section on Patient 
Withdrawal) ............................................................................................................ 148 
8.13. Eliciting Adverse Event Information .................................................................. 149 
8.14. Reporting Requirements ..................................................................................... 149 
8.14.1. Serious Adverse Event Reporting Requirements ................................... 149 

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8.14.2. Non-Serious Adverse Event Reporting Requirements ............................ 149 
8.14.3. Sponsor’s Reporting Requirements to Regulatory Authorities ............... 149 
9. DATA ANALYSIS/STATISTICAL METHODS ............................................................. 150 
9.1. Analysis Sets .......................................................................................................... 150 
9.2. Statistical Methods and Properties ........................................................................ 151 
9.2.1. Methods ..................................................................................................... 151 
9.2.2. Simulations for CRM Design in Phase 1 ................................................... 152 
9.3. Sample Size Determination ................................................................................... 153 
9.4. Efficacy Analysis ................................................................................................... 155 
9.4.1. Primary Analysis ....................................................................................... 155 
9.4.2. Analysis of Secondary Endpoints ............................................................. 156 
9.4.3. Analysis of Exploratory Endpoints ........................................................... 158 
9.5. Analysis of Other Endpoints .................................................................................. 159 
9.5.1. Analysis of Pharmacokinetics ................................................................... 159 
9.5.1.1. Single- and Multiple-Dose PF-06463922 PK Analysis ........... 159 
9.5.1.2. Effect of PF-06463922 on MDZ Pharmacokinetics ................ 159 
9.5.1.3. Effect of Food on PF-06463922 Pharmacokinetics ................. 160 
9.5.1.4. Population Pharmacokinetic Analysis or PK/PD Modeling .... 160 
9.5.1.5. Metabolite Profiling ................................................................. 160 
9.5.1.6. Statistical Analysis of Biomarker Endpoint ............................ 160 
9.6. Safety Analysis ...................................................................................................... 160 
9.6.1. Analysis of Primary Endpoint for Phase 1 ................................................ 161 
9.6.2. Analysis of Secondary Safety Endpoints for Phase 1, Phase 2, and 
the DDI/Holter monitoring study ................................................................... 161 
9.6.3. ECG Analysis ............................................................................................ 162 
9.7. Pharmacodynamic Analysis ................................................................................... 162 
9.8. Patient Reported Outcomes Analyses .................................................................... 163 
9.9. Cognitive, Mood and Suicidal Ideation and Behavior Analyses (Phase 
2 only) ...................................................................................................................... 163 
9.10. Japanese Patient-Only Lead In Cohort (Japan Sites Only) .................................. 163 
9.11. Patients Receiving Crizotinib after PF-06463922 ............................................... 164 
9.12. Drug-drug Interaction and Holter Monitoring Study (Phase 2) .......................... 164 
9.13. Data Safety Monitoring Committee ..................................................................... 165 

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9.14. Independent Central Radiological Review .......................................................... 165 
10. QUALITY CONTROL AND QUALITY ASSURANCE ............................................... 166 
11. DATA HANDLING AND RECORD KEEPING ............................................................ 166 
11.1. Case Report Forms/Electronic Data Record ........................................................ 166 
11.2. Record Retention ................................................................................................. 167 
12. ETHICS ............................................................................................................................ 167 
12.1. Institutional Review Board (IRB)/Independent Ethics Committee (IEC) ........... 167 
12.2. Ethical Conduct of the Study ............................................................................... 167 
12.3. Patient Information and Consent ......................................................................... 168 
12.4. Patient Recruitment ............................................................................................. 168 
12.5. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH 
GCP .......................................................................................................................... 168 
13. DEFINITION OF END OF TRIAL ................................................................................. 169 
14. SPONSOR DISCONTINUATION CRITERIA ............................................................... 169 
15. PUBLICATION OF STUDY RESULTS ........................................................................ 169 
15.1. Communication of Results by Pfizer ................................................................... 169 
15.2. Publications by Investigators ............................................................................... 170 
16. REFERENCES ................................................................................................................. 171 
 
LIST OF TABLES 
Table 1. 
Reduced Schedule of Assessments upon approval of Amendment 8 ...... 25 
Table 2. 
Phase 1 Portion of the Study .................................................................... 28 
Table 3. 
Phase 1 Portion of the Study Pharmacokinetic Assessments ................... 33 
Table 4. 
Phase 2 Portion of the Study .................................................................... 35 
Table 5. 
Phase 2 Portion of the Study - Pharmacokinetic Assessments (Not 
Applicable for Patients in the DDI and Holter Study) ............................. 41 
Table 6. 
Drug-Drug Interaction and Holter Monitoring Study .............................. 43 
Table 7. 
Grade ≥2 Treatment-Related CNS Effects in Phase 1 ............................. 68 
Table 8. 
Grade ≥2 Treatment- Related Peripheral Neuropathy Events in 
Phase 1 ..................................................................................................... 68 
Table 9. 
Phase 1 PF-06463922 Dose Levels .......................................................... 92 
Table 10. 
PF-06463922 Dose Modifications for PF-06463922-Related 
Toxicities ................................................................................................ 112 

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Table 11. 
Phase 1 PF 06463922 QD Dose Level Reductions ................................. 116 
Table 12. 
Phase 2 PF 06463922 QD Dose Level Reductions ................................. 116 
Table 13. 
PF-06463922 BID Dose Levels (Phase 1) .............................................. 116 
Table 14. 
Pharmacokinetic Properties of Statins .................................................... 123 
Table 15. 
Pharmacokinetic Properties of Lipid Lowering Agents .......................... 123 
Table 16. 
Summary of Biomarker Assessments ..................................................... 136 
Table 17. 
Probability of DLT as a Function of Dose .............................................. 152 
Table 18. 
Operating Characteristics of the CRM in Phase 1 .................................. 153 
Table 19. 
Estimated ORRs and Related 95% Confidence Intervals ....................... 154 
Table 20. 
Response Evaluation Criteria in Solid Tumors ....................................... 181 
Table 21. 
Dose Modifications for Crizotinib .......................................................... 201 
Table 22. 
Crizotinib Dose Modifications for Treatment-Related Toxicity ............. 202 
Table 23. 
Schedule of Assessments for Patients Receiving Crizotinib 
Following PF-06463922 .......................................................................... 205 
 
 
LIST OF FIGURES 
Figure 1. 
Study Schema ........................................................................................... 83 
Figure 2. 
Japanese Patient-Only Lead-In Cohort Schema ....................................... 89 
 
 
APPENDICES 
Appendix 1. Phase 1 Required Laboratory Assessments ...................................................... 175 
Appendix 2. Phase 2 Required Laboratory Assessments ...................................................... 176 
Appendix 3. RECIST (Response Evaluation Criteria in Solid Tumors) v1.1 Modified to 
Include Assessment of CNS Metastases ................................................ 177 
Appendix 4. ECOG Performance Status ............................................................................... 183 
Appendix 5. Bone Marrow Reserve in Adults ...................................................................... 184 
Appendix 6. EORTC QLQ-C30 Questionnaire ..................................................................... 185 
Appendix 7. EORTC QLQ-LC13 Questionnaire .................................................................. 187 
Appendix 8. Mini Mental State Examination ........................................................................ 188 
Appendix 9. Japanese Patient-Only Lead-In Cohort (LIC) Schedule of Assessments .......... 189 
Appendix 10. Safety Review Process for Japanese Only Patient LIC .................................. 195 
Appendix 11. Patients Receiving Crizotinib Following PF-06469322 ................................. 196 

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Appendix 12. Drugs Known to Prolong PR Interval ............................................................. 207 
Appendix 13. Country Specific Appendix for France ............................................................ 208 

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1. INTRODUCTION 
1.1. Indication 
Anaplastic Lymphoma Kinase (ALK)-positive (ALK+) or ROS oncogene 1 (ROS1)-positive 
(ROS1+) advanced non-small cell lung cancer (NSCLC). 
1.2. Background 
Lung cancer has been the most common cancer in the world for several decades, and by 
2008, there were an estimated 1.61 million new cases, representing 12.7% of all new cancers. 
It was also the most common cause of death from cancer, with 1.38 million deaths (18.2% of 
the total). Non small cell lung cancer (NSCLC) constitutes approximately 85% of all lung 
cancer.1 
In 2007, two research groups independently reported the discovery of an NSCLC oncogenic 
fusion gene (EML4-ALK) that combines portions of the echinoderm microtubule-associated 
protein- like 4 (EML4) gene and the anaplastic lymphoma kinase (ALK) gene.2,3 This fusion 
gene encodes for the cytoplasmic fusion protein EML4-ALK which upon dimerisation, 
results in constitutive activation of the kinase domain of ALK. ROS 1 fusions were 
identified as potential driver mutations in a NSCLC cell line (HCC78: SLCA2-ROS1) and a 
NSCLC patient sample (CD74-ROS1).3 Approximately 3-5% of NSCLC is histologically 
defined as ALK+4 and 1-2% ROS1+5 The vast majority of ALK and ROS1 fusion positive 
cases were observed in young, non-smoking patients with lung adenocarcinoma, and are 
rarely coincident with each other, and with EGFR, HER2, or KRAS mutations.6 
1.2.1. Efficacy of Targeted Inhibitors in Patients with ALK+ [rearrangement (WT) and 
resistance mutations (mu)] and ROS1+ NSCLC 
Crizotinib, a potent and selective Adenosine triphosphate (ATP) competitive inhibitor of 
c-MET, ALK and ROS 1 receptor tyrosine kinases and relevant oncogenic variants, was first 
studied clinically in ALK+ NSCLC in an ongoing Phase 1 trial soon after the discovery of 
the EML4-ALK fusion protein oncogenic driver potential in NSCLC.7 The clinical benefit of 
crizotinib led to the US approval in August 2011 of XALKORI (crizotinib) in advanced 
ALK+ NCSLC patients. Crizotinib as single agent in previously treated ALK+ NSCLC 
patients demonstrated a median progression-free survival 7.7 months versus in the crizotinib 
group and 3.0 months in the chemotherapy (docetaxel or pemetrexed). The Objective 
Response Rates (ORR) were 65% (95% confidence interval (CI), 58 to 72) with crizotinib, as 
compared with 20% (95% CI,14 to 26) with chemotherapy (P<0.001)16 Crizotinib has also 
demonstrated activity in ROS1-positive NSCLC patients.15 In a series of 35 patients with 
ROS1+ NSCLC, of 25 evaluable patients an ORR of 60% was reported, 6-month PFS 
probability was 71% (95% CI: 45.6–86.0). 
Although most patients with ALK+ NSCLC derive substantial clinical benefit from 
crizotinib, some ALK+ NSCLC patients will not derive any benefit (intrinsic resistance) 
while other patients who initially derived benefit may later develop resistance (acquired 
resistance). The pattern of ROS1 acquired resistance is still emerging but mutations in the 
kinase domain are similarly considered likely to contribute to the observed resistance to 
ROS1 inhibitor treatment.17 

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Unlike acquired resistance to EGFR inhibitor where T790M gatekeeper mutation accounts 
for approximately all secondary mutation-driven resistance cases, and 50% of all 
resistance,8 the resistance to ALK inhibitors appears much more complex as a greater variety 
of mutations are found in patients along with the activation of bypass resistance 
mechanisms.11,9 To date, multiple types of ALK kinase domain mutations have been 
identified in crizotinib refractory patients including ALKg1269a, ALKl1196m, ALKc1156y, 
ALKl1152r, ALKf1174l, ALK g1202r, ALKs1206y, ALK1151tins and ALK gene amplification,9,12,21 and 
account for about one third of resistant samples tested. Among these ALK mutations, 
ALKg1202r conferred high-level resistance to almost all of the ALK inhibitors tested.9,12,21 In 
the case of crizotinib resistant ALK+ NSCLC patients, the rate of resistance due to mutations 
in the ALK kinase domain is typically reported in the range of 35-40%.8 While other 
mechanisms of resistance (independent of ALK mutation) are active, the tumor cell may still 
remain dependent upon ALK signaling. It was also reported that the brain was the most 
common single site of disease progression (>30%) following initial crizotinib 
treatment.13,14 It is unknown if this is due to the formation of resistance mutations or the 
intact blood brain barrier (BBB) creates a sanctuary site preventing the passage of crizotinib. 
Finally another roughly 5% of patients acquire resistance through amplification of the 
EML4-ALK fusion gene.9 
Several investigational agents targeting ALK and ROS1 are now in clinical trials. These 
agents, mostly small molecule tyrosine kinase inhibitors, have reported anti-tumor activity in 
both ALK+ wild type and mutated NSCLC. Preliminary data of those most advanced in 
clinical trials to date report ORRs of 70-85% in patients with ALKinhibitor treatment naïve 
ALK+ NSCLC and in patients with ALK+ NSCLC relapsed after ALK inhibitor 
treatment.18,19,20 While there are other compounds being evaluated no ALK nor 
ROS1 targeted TKI has demonstrated curative results and additional drugs are needed to 
overcome resistance mechanisms, to impact patient outcomes through improved response 
rates and PFS and significiant anti-tumor activity on CNS metastases. 
1.3. PF-06463922 
1.3.1. PF-06463922 Background 
PF-06463922 is a selective, ATP-competitive small molecule tyrosine kinase inhibitor of the 
ALK and ROS1 (c-ROS oncogene 1) receptor tyrosine kinases (RTK) that also potently 
inhibits ALK kinase domain mutations responsible for resistance to crizotinib. Oncogenic 
fusions of ALK and ROS1 define two distinct subsets of human lung adenocarcinoma 
patients and play essential roles in regulation of tumor cell survival, growth and 
metastasis.2,5 
In cell assays, PF-06463922 inhibited ALK kinase activity (measured by inhibition of its 
autophosphorylation) with cell IC50’s of 1.5 nM and 21 nM for EML4-ALK and 
EML4-ALK (L1196M), the most common mutation that occurs within the gatekeeper residue 
of the ALK kinase, which compares favourably to crizoitinib IC50’s of 80 nM and 841 nM, 
respectively). Data from in vivo efficacy models bearing the EML4-ALK (L1169M] 
mutation predicted the efficacious concentration (Ceff) to be 51 nM (unbound), which 
corresponds to achieving tumor stasis (100% tumor growth inhibition) in this preclinical 

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model. In the 3T3-EML4-ALKG1202R model for the G1202R EML4-ALK mutation, 80% 
tumor growth inhibition was seen at Ceff of 125 nM (unbound), which corresponds to 
150 ng/mL total concentration. 
PF-06463922 has been studied in a variety of in vitro and in vivo model systems to determine 
potency for inhibition of ALK or ROS1 tyrosine kinase activity, kinase selectivity, 
anti-tumor efficacy, pharmacokinetic (PK)/pharmacodynamic (PD) relationships, and 
mechanism of action. In vitro, PF-06463922 demonstrated potent, concentration-dependent 
inhibition in catalytic activities of ALK, ALK mutants and ROS1 kinases in recombinant 
enzyme and cell based assays. PF-06463922 also inhibited ALK and ROS1 dependent 
oncogenic functions in human NSCLC cell lines, and demonstrated potent and selective 
growth inhibitory activity and induced apoptosis in tumor cell lines exhibiting either 
non-mutant ALK and ROS1 fusion variants or mutant ALK fusions that are acquired and 
resistant to crizotinib treatment. 
In vivo, PF-06463922 demonstrated marked cytoreductive activity in mice bearing tumor 
xenografts that express ALK or ROS1 fusion variants, including the crizotinib resistant 
EML4-ALKL1196M or EML4-ALKG1269A mutations. 
PF-06463922 treatment significantly reduced the tumor size and prolonged animal survival 
in the orthotopic brain models (EML4-ALK and EML4-ALKL1196M) in mice. The anti-tumor 
efficacy of PF-06463922 was dose dependent and demonstrated strong correlations to 
inhibition of ALK or ROS1 phosphorylation. The plasma levels associated with inhibitory 
activity of PF-06463922 against EML4-ALKL1196M phosphorylation and anti-tumor efficacy 
in EML4-ALKL1196M dependent human NSCLC cell line models was utilized to project target 
human plasma concentrations for clinical studies. The Ceff (unbound) for EML4-ALK, 
EML4-ALKL1196M, and EML4-ALKG1202R of 6.5nM, 51 nM, and 125 nM, respectively, when 
corrected for human plasma protein binding results in Ceff (total) of 7.6 ng/mL, 62 ng/mL, 
and 150 ng/mL, respectively. 
More details of the complete in vitro and in vivo efficacy package may be found in the 
PF-06463922 Investigator’s Brochure.22 
The single safety reference document for midazolam is the United States package insert 
USPI for Midazolam Hydrocholoride supplied by Paddock Laboratories, Inc., Minneapolis, 
MN.41 
1.3.2. PF-06463922 Pre-Clinical Safety Data 
1.3.2.1. Pancreas 
Pancreatic toxicity was observed in the rat and dog repeat dose studies. Severity was 
dose-related and ranged from minimal to marked. With increased severity, the changes were 
more diffuse and pancreatic exocrine tissues became affected such that intralobular fibrous 
tissue appeared more prominent. The pancreatic changes observed with PF-06463922 did 
not elicit an acute inflammatory response, though scattered minimal mononuclear or mixed 
cell infiltrates were occasionally present. While minor elevations (<1-fold) in mean amylase 
and lipase levels were identified in the rat, there was no clear correlation to the pancreatic 

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lesions. Minor elevations (minimal or mild) in amylase and lipase (<1-fold) in the dog were 
not associated with minimal or mild pancreatic lesions; however, moderate to high amylase 
and lipase elevations (4- and 8-fold, respectively) were found to coincide with pancreatic 
acinar atrophy in the dog and included more prominent single cell necrosis in the absence of 
inflammation. Elevations in glucose and cholesterol (up to 2.2-fold) were observed in rat and 
dog studies; however, these were small in magnitude, without historical reference range, or 
lacked histological correlates and were therefore considered non-adverse and without 
toxicological significance. At the end of a 1-month non-dosing period, all clinical chemistry 
parameters were comparable to control values (except cholesterol), and full to partial 
recovery of the pancreatic lesions was observed in both the rat and dog. Pancreatic changes 
were considered minimal or mild at 8 mg/kg/day in male rats. One month dosing (up to 
25 mg/kg/day) is associated with low severity pancreatic findings in dogs. Furthermore due 
to the known occurrence of spontaneous lesions of comparable severity in Beagle dogs, a 
safety margin 12-fold over the predicted minimal efficacious dose in humans (10 mg BID, 
based on an unbound AUC comparison) is estimated for PF-06463922 (499 ng49/mL) A no 
effect level was identified at 2 mg/kg/day in male rats and was not identified in dogs 
(<2 mg/kg/day) following 1 month of dosing (<2-fold margin based on a comparison of 
unbound AUC to that projected at the minimal efficacious dose in humans at 10 mg BID). 
1.3.2.2. Liver 
Liver effects were identified following 14 days and 1 month of dosing in the rat. Liver 
enzyme (ALT, AST, ALP, GLDH, and/or GGT; up to 5-fold control) and total bilirubin 
elevations correlated with hepatocellular hypertrophy, single cell necrosis, and/or bile duct 
hyperplasia in the rat at 15 mg/kg/day. Increased sinusoidal cells were also observed in 
male rats at 60 mg/kg/day following 14 days of dosing. A no effect level for liver effects 
was identified at 8 and 4 mg/kg/day in male and female rats, respectively, providing a 12- to 
14-fold margin over the predicted minimal efficacious exposure in humans at 10 mg BID 
based on an unbound AUC comparison. 
1.3.2.3. Hematopoietic 
Hematopoietic effects were observed in the rat and dog, primarily reflected by an effect on 
the erythron that elicited a regenerative erythropoietic response. Decreases in red blood cell 
parameters (RBC count, hematocrit, hemoglobin) up to 30% compared to control were 
observed at 2 mg/kg/day in the rat and dog following 14 days and 1 month of dosing, 
respectively. The observed erythroid effects provide safety margins from the 1-month 
studies of up to 60-fold based on a comparison of unbound AUC to that projected at the 
minimal efficacious dose in humans at 10 mg BID. Increases in white blood cell (up to 
8-fold; white blood cell counts, lymphocytes, neutrophils, monocytes, large unstained cells) 
were noted. Slight increase in platelets was observed suggesting a a collateral effect from 
RBC regeneration. 

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1.3.2.4. Cardiovascular 
Cardiovascular changes (blood pressure, heart rate) and secondary effects on cardiac 
parameters were identified in telemetered rats and dogs following single- and/or repeat-doses 
(up to 19 days). Increases or decreases in blood pressure (up to 37 mmHg systolic, diastolic, 
and mean) were observed in the rat and dog at 10 mg/kg/day. Heart rate was also altered at 
10 mg/kg/day, characterized by a biphasic response in the rat with an initial decrease of up 
to 36 bpm and subsequent increase of up to 32 bpm (12 to 15 hours post dose), whereas an 
increase in heart rate was identified in the dog (up to 17 bpm). The differences in 
cardiovascular profiles between rats and dogs for both blood pressure and heart rate 
parameters may reflect a species-specific response to PF-06463922, but are considered 
indicative of the potential for a cardiovascular effect. Observed changes are believed to 
reflect compensatory mechanisms versus a direct effect on heart tissue. Reversal of effects 
on electrocardiogram (ECG) intervals and blood pressure was demonstrated following a 
5- day non-dosing interval in the dog. 
1.3.2.5. Cognition and Neurological Function 
PF-06463922 was shown to be a brain penetrable compound, with measurable levels in the 
brain and cerebral spinal fluid (CSF) in the rat. The potential for central nervous system 
(CNS) effects and cognitive deficit were suggested from safety pharmacology and general 
toxicity studies. Functional observational battery (FOB) assessments included in a 14-day 
repeat-dose toxicity study in the rat identified CNS effects, including abnormal behavior (ie, 
teeth chattering), involuntary movements (ie, retropulsion and trembling), reduced handling 
reactivity, decreased arousal, abnormal gait, and reduced reflex responses (ie, uncoordinated 
air righting-reflex, and reduced extensor thrust response) at 60 mg/kg/day. It is unclear 
whether the observations were due to a direct effect on the CNS or secondary to a general 
lack of tolerance to PF-06463922 administration; however, the FOB findings were primarily 
observed in moribund animals. In addition, CSF and brain concentrations (up to 319 ng/mL 
and 40.5 ng/mL, respectively) achieved at this dose suggest that concentrations well 
exceeding primary pharmacology were reached (wild-type cell-based ALK IC50 0.6 ng/mL). 
A pharmacology-driven effect, however, cannot be completely ruled out given that ALK 
expression has been demonstrated in the brain of mice, where it is thought to play an 
important role in brain development and function.23,24,25 As such, it is possible that the CNS 
effects are a result of ALK inhibition in the brain. No FOB effects were identified in the 
definitive assessment following 26 days of dosing at doses up to 30 mg/kg/day, despite 
achieving comparable plasma concentrations, providing a 59-fold margin over the predicted 
minimal efficacious exposure in humans at 10 mg BID based on an unbound Cmax 
comparison. 
The potential for an effect on cognitive function was suggested from an ex vivo hippocampal 
brain slice assay and an exploratory in vivo model, the rat contextual renewal model. 
PF-06463922 caused a significant reduction in amplitude of long term potentiation, a 
measure that is widely considered as one of the cellular mechanisms that underlie learning 
and memory formation.26 This effect was observed at 1 M (406 ng/mL) but not at 100 nM 
(41 ng/mL). In the contextual renewal model, a decrease in memory recall and cue-induced 
renewal responding was observed at 3 mg/kg, though variability in the pharmacologic 

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sensitivity was identified with both the tool compound used for validation, as well as with 
PF-06463922. The variable response with PF-06463922 was observed at 3 mg/kg, a dose 
where relevant brain concentrations (262 ng/mL) were achieved for inhibition of wild-type 
ALK (cell-based IC50 0.52-0.98 ng/mL) and TrkB (cell-based IC50 93 ng/mL). 
As TrkB receptors have been implicated in synaptic plasticity, long term potentiation, as well 
as memory processes in rats,27 the results with PF-06463922 may reflect a potential to affect 
cognitive function that is driven by secondary pharmacology at the TrkB receptor; however, 
these results cannot be used to assess safety margins relevant to human exposure due to the 
exploratory nature and variability in sensitivity of the model. 
1.3.2.6. Gastrointestinal 
Clinical signs of gastrointestinal effect, and stomach and intestinal findings were observed in 
the rat and dog in 14-day toxicity studies. Clinical signs of emesis in dogs and abnormal 
feces (soft, watery, and/or mucoid) in rats and dogs observed acutely and following multiple 
doses were considered mild in the absence of a significant effect on body weight or clinical 
toleration. There were no PF-06463922-related stomach changes in the dog. Minimal or 
mild single cell necrosis in the gastric glands of the pyloric stomach was observed at the 
highest doses tested in rats (30 mg/kg/day in males and 15 mg/kg/day in females) following 
1 month of dosing. Full recovery was shown following a 1-month non-dosing period. There 
were no PF-06463922-related microscopic effects in the stomach or intestines of rats or dogs 
following 1 month of dosing at doses up to 30 and 25 mg/kg/day, respectively, providing up 
to a 60-fold margin over the predicted minimal efficacious exposure in humans at 10 mg BID 
based on an unbound AUC comparison. 
1.3.2.7. Effects on the Skin 
Skin effects were identified in the rat following repeat-dosing at 15 mg/kg/day. Following 
1 month of dosing, gross findings of wound, scar, or crust on skin of the head, neck or limbs 
were characterized microscopically by erosion, ulcer or dermal fibrosis at 30 mg/kg/day in 
male rats and 15 mg/kg/day in female rats. Dermal fibrosis was considered consistent with 
resolution of the erosion or ulcer. Skin findings were not present following a 1-month 
non-dosing period. 
1.3.2.8. Effects on the Thymus 
Effects on the thymus were observed in the dog following 14 days and 1 month of dosing. 
An increased incidence of decreased lymphoid cellularity (minimal to moderate) was 
observed in the thymus at 25 mg/kg/day in male dogs following 1 month of dosing. 
Decreased thymic weights corresponded with this histological change in some animals given 
that 25 mg/kg/day was a non-severely toxic dose, a direct effect of PF-06463922 cannot be 
out ruled. Partial recovery was observed after a 1-month non-dosing period. 

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1.3.2.9. Inflammatory Response 
Increases in white blood cell (up to 8-fold; white blood cell counts, lymphocytes, neutrophils, 
monocytes, large unstained cells), increased fibrinogen (up to 6-fold), and clinical chemistry 
parameters (up to 54%; increased globulin, decreased albumin) suggestiveof an inflammatory 
response were observed in the rat and dog following acute exposure (dog) and 14 days and/or 
1 month of repeat-dosing at 2 mg/kg/day. An increase in myeloid cellularity (minimal to 
mild) in the bone marrow correlated with this inflammatory response following 1 month of 
dosing at 2 mg/kg/day in dogs. While there was generally no clear source of the 
inflammatory response, inflammation was sporadically noted on the skin of rats with 
erosion/ulcer or dermal fibrosis at 30 mg/kg/day (males) and 15 mg/kg/day (females) in 
1- month toxicity study. With the exception of residual clinical chemistry changes at 
25 mg/kg/day in male dogs, full recovery was observed following a 1-month non-dosing 
period in the rat and dog. 
1.3.2.10. Effects on Peripheral Nerves 
Minimal axon degeneration in the peripheral nerve was identified in rats following 1 month 
of dosing at 30 mg/kg/day in males and 15 mg/kg/day in females. This change was 
characterized by swollen and hypereosinophilic axons in clear vacuoles and occasional 
formation of digestion chambers. No active axon degeneration was identified following a 
1- month non-dosing period, suggesting the reversible nature of this finding when the 
neuronal soma is viable. 
1.3.2.11. Teratogenicity 
Preliminary developmental toxicity studies using PF-06463922 have been completed in rats 
and rabbits. Embryonic and fetal toxicity (including embryo lethality, fewer and smaller 
viable fetuses with some external and visceral malformations) was observed in both species 
at all doses, where the low dose was projected to yield similar exposure as the recommended 
Phase 2 dose of 100 mg once daily. 
For more details about the preclinical safety profile of PF-06463922, refer to the 
Investigator’s Brochure (IB).22 
1.3.3. PF-06463922 Clinical Trial Experience 
PF-06463922 has been administered to 54 patients in the Phase 1 part of this study across 
7 once daily (QD) doses of 10 mg, 25 mg, 50 mg, 75 mg, 100 mg, 150 mg, and 200 mg and 
3 twice daily (BID) doses of 35 mg BID, 75 mg BID, and 100 mg BID. As described in 
Section 3.4.3, a continual reassessment method (CRM) model was used in Phase 1 to 
determine which dose(s) to test based on the DLTs observed during Cycle 1. The CRM was 
initiated at 25 mg QD and recommended escalation to 75 mg QD, 150 mg QD, and 200 mg 
QD based on no DLTs observed at the previous dose levels tested. At 200 mg QD, one (1) 
DLT occurred in a patient who failed to receive 16 of the planned 21 doses of 
PF-06463922 due to Grade 1 and Grade 2 CNS effects. Although the CRM model 
recommended continuation to the next higher dose above 200 mg QD, a decision was made 
among the treating investigators and the sponsor to re-test lower doses (ie, outside of the 

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CRM model) to better understand and evaluate the CNS effects observed at the higher dose 
levels. The protocol was amended at that time (Amendment 3) to formalize testing doses 
outside of the CRM model and to evaluate BID dosing and effects of food on PF-06463922. 
Lower doses of 50 mg QD, 75 mg QD, and 100 mg QD were also evaluated. BID doses 
tested included 35 mg BID, 75 mg BID, and 100 mg BID. A food effect cohort was tested at 
100 mg QD (3 patients in fed/fasted state and 3 patients in fasted/fedstate). Finally, a CSF 
sampling cohort was tested at 100 mg QD to obtain preliminary information about 
PF-06463922 penetration in the brain. 
Overall, PF-06463922 was well tolerated in Phase 1. As of the data cutoff date for 
Amendment 4 (15 June 2015), the most commonly occurring treatment-related adverse 
events across all of the doses tested in Phase 1 were hypercholesterolemia (64%), CNS 
effects (36%), peripheral oedema (32%), peripheral neuropathy (28%), and 
hypertriglyceridemia (26%). The most frequently occurring treatment-related Grade 
≥3 adverse events were hypercholesterolemia (10%) and hypertriglyceridemia (4%). 
Because the adverse events were varied in their presentation and description, higher level 
(“cluster”) terms (ie, CNS effects and peripheral neuropathy, etc.) were used to further 
describe the safety profile of PF-06463922. A breakdown of the specific preferred terms that 
comprise these higher level terms can be found in the Investigator’s Brochure. 
Dosing interruptions and dose reductions were reported in 9 (18%) and 18 (36%) of patients, 
respectively. Most of these delays and reductions occurred at doses higher than 100 mg QD 
and the most common reasons for dosing interruption and/or dose reduction at these higher 
doses were hypercholesterolemia and CNS effects. 
A total of 5 patients had treatment-related serious adverse events; 3 of them had CNS events 
that included Grade 2 hallucinations and Grade 2 seizure in 1 patient (150 mg QD); 
Grade 2 seizure in a second patient (75 mg BID), and mental status changes in a third patient 
(150 mg QD). In addition, 1 patient (150 mg QD) had Grade 3 dermatomyositis, and 
1 patient (100 mg QD) had Grade 3 lipase increased. No Grade 4 or 
Grade 5 treatment-related SAEs were reported. There were neither any adverse events that 
led to treatment discontinuation, nor any treatment-related deaths. 
Treatment-related CNS effects were observed in 18 (36%) Phase 1 patients. These events 
were considered mild (Grade 1 and Grade 2), transient, and were most commonly reported 
after Cycle 3; however, at the higher dose levels (≥150 mg QD), these events occurred earlier 
on. These events were reversible upon dosing interruption and/or dose reduction, and no 
patients were permanently discontinued due to these events. A summary of Grade 2 and 
higher individual CNS effect preferred terms, including the dose at which they occurred and 
whether or not they required a dose modification, are described below in Table 7. 
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Table 7. 
Grade ≥2 Treatment-Related CNS Effects in Phase 1 
 
Preferred Term 
Toxicity Grade 
Dose at 
Which AE 
Occurred 
Dose Modification Required 
Cognitive Disorder 
2 
200 mg QD 
Dose Delay and Dose Reduction 
Aphasia 
2 
200 mg QD 
Dose Delay and Dose Reduction 
Hallucination 
2 
150 mg QD 
Dose Delay 
Hallucination 
2 
150 mg QD 
Dose Delay 
Irritability 
2 
200 mg QD 
Dose Delay and Dose Reduction 
Mental status changes 
3 
150 mg QD 
Dose Delay 
Seizure 
2 
100 mg QD 
Dose Delay 
Seizure 
2 
75 mg BID 
Dose Delay 
Visual Impairment 
2 
100 mg QD 
Dose Reduction 
 
Treatment-related increases in lipids, including cholesterol and triglycerides, were observed 
in 32 (64%) and 13 (26%) of Phase 1 patients, respectively. The majority of these elevations 
were Grade 1 and Grade 2 in severity and well managed with the use of a statin or other 
lipid-lowering agent. Lipid testing was added later in the study (ie, introduced in 
Amendment 3), and thus, there are limited data on patients treated at earlier cycles on the 
initial doses; however, these laboratory abnormalities have been observed at all of the Phase 
1 dose levels tested. There have been no associated cardiovascular changes. 
Peripheral neuropathy was observed in 14 (28%) Phase 1 patients. These events were 
completely reversible upon dosing interruption and/or dose reduction. A summary of 
treatment-related Grade ≥2 individual peripheral neuropathy preferred terms, including the 
dose at which they occurred and whether or not they required a dose modification, are 
presented below in Table 8. Grade 1 individual peripheral neuropathy preferred terms can be 
found in the Investigator’s Brochure. 
Table 8. 
Grade ≥2 Treatment- Related Peripheral Neuropathy Events in Phase 1 
 
Preferred Term 
Toxicity Grade 
Dose at 
Which AE 
Occurred 
Dose Modification Required 
Neuropathy peripheral 
2 
75 mg QD 
None 
Neuropathy peripheral 
2 
100 mg QD 
None 
Paraesthesia 
2 
150 mg QD 
None 
Neurotoxicity 
2 
100 mg QD 
None 

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Treatment-related peripheral edema was observed in 16 (32%) Phase 1 patients. These 
events were manageable and reversible upon dosing interruption and/or dose reduction. 
In terms of preliminary efficacy in Phase 1, PF-06463922 demonstrated robust clinical 
activity, although these patients represent a heterogeneous mix of driver mutations, prior 
treatments, and dose levels at which they were treated. Among 43 patients evaluable for 
efficacy as of the data cutoff date (15 June 2015) for Amendment 4, the ORR was 37% 
comprising 1 confirmed CR (2.3%) and 15 (35%) confirmed PRs. Further, 10 (23%) patients 
had SD as their best overall response. The response rate appeared similar whether patients 
had 1 or 2 prior TKIs. 
Thirty-four (69%) patients had CNS metastases at study entry. Of the 30 patients evaluable 
for intracranial response at the time of the data cut-off, 4 (13%) patients had a confirmed 
intracranial CR and 5 (17%) patients had a confirmed intracranial PR. Further, 10 (33%) 
patients had intracranial SD as their best CNS response. 
Taken together, these preliminary efficacy results from Phase 1 suggest robust anti-tumor 
activity and brain penetration which should be further characterized in Phase 2. 
1.3.4. Benefit/Risk Assessment 
Non-Clinical 
The nonclinical safety profile of PF-06463922 has been extensively evaluated in vitro, 
ex vivo, and in vivo in the rat and dog to support progression into clinical trials in advanced 
cancer indications. The primary target organ effects were observed on the pancreas, liver, 
hematopoietic and cardiovascular systems, and peripheral nerve. Additional effects were 
observed on male reproductive organs, cognitive performance and neurological function, the 
gastrointestinal system, and skin. The potential for reversibility of the target organ toxicities 
was established following a 1-month non-dosing period. PF-06463922 is also a potential 
phototoxicant based on Ultra Voilet –B (UVB)-absorbing properties, and an aneugen but not 
a mutagen. The nonclinical safety findings related to PF-06463922 administration represent 
toxicities that can be monitored and are considered clinically manageable or acceptable risks 
in the intended patient population. 
The nonclinical efficacy profile of PF-06463922 has been extensively investigated in a series 
of relevant preclinical disease models in vitro and in vivo. PF-06463922 potently inhibited 
its kinase targets (ALK, ALK mutants and ROS1) in recombinant enzyme and cell assays, 
and demonstrated inhibitory effects against ALK-, mutant ALK- and ROS1-dependent 
cancer phenotypes including tumor cell proliferation and survival. 
In vivo, PF-06463922 demonstrated marked cytoreductive activity in mice bearing tumor 
xenografts that express ALK or ROS1 fusion variants, including the crizotinib resistant 
EML4-ALKL1196M or EML4 ALKG1269A mutations. PF-06463922 treatment 
significantly reduced the tumor size and prolonged animal survival in the orthotopic brain 
models harboring either EML4-ALK or EML4 ALKL1196M in mice. The anti-tumor efficacy 
of PF-06463922 was dose dependent and demonstrated strong correlations to inhibition of 

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ALK or ROS1 phosphorylation, and there was no body weight loss observed in any of the in 
vivo efficacy studies. Collectively the data indicate that PF-06463922 is a potent inhibitor of 
ALK and ROS1 kinase. It is capable of inhibiting all clinically reported crizotinib resistant 
ALK fusion mutants at pharmacologically relevant concentrations, including the 
ALKG1202R mutation that is resistant to almost all of the ALK inhibitors tested to date. 
Additionally, it regressed both non-mutant and mutant ALK fusion positive tumors in the 
orthotopic brain models. Therefore the benefit to risk assessment is in favor of studying 
PF-06463922 in patients with advanced ALK+ NSCLC or advanced ROS1+ NSCLC and 
within those patient groups, to also assess the anti tumor activity of PF-06463922 on CNS 
metastases. 
Clinical 
The clinical safety and efficacy profile of PF-06463922 as observed in Phase 1 patients 
indicated that PF-06463922 is overall well tolerated and demonstrated robust clinical activity 
(ORR of 37%) and brain penetration (CNS response rate of 30%). As described in 
Section 1.3.3, the most commonly occurring treatment-related adverse events in 
Phase 1 were effects on lipids, effects on CNS, peripheral edema, and effects on peripheral 
nerves. These events were considered manageable and reversible upon dosing interruption 
and/or dose reduction. Patients in Phase 2 will be closely monitored for these effects; lipids 
will be routinely collected, and patients will be advised to initiate the use of a statin or other 
lipid-lowering agent early in order to prevent further increases (see Table 14 and Table 15 in 
Section 5.3.2.6). Additionally, patients will be assessed for changes in cognitive function or 
mood and any potential suicidal ideation or behavior. 
The benefit/risk assessment remains favorable for continuing the development of 
PF-06463922 in patients with advanced ALK+ NSCLC or advanced ROS1+ NSCLC with or 
without CNS metastases. 
1.3.5. Safety Considerations in the Clinical Trial 
Pancreatic acinar atrophy was identified in 14-day ETS and 1-month regulatory toxicology 
studies in both rodent and non-rodent species Minimal to mild findings at clinically relevant 
concentrations are non-adverse (mid dose in rats and all doses in dogs from 1-month study). 
The pathogenesis is considered distinct from acute pancreatitis, no inflammation nor necrotic 
cell death were observed. Published literatures report amylase and lipase as having high 
variability as biomarkers, but supplemented with clinical signs and symptoms monitored with 
abdominal radiology, their monitoring can still support clinical dose modification decision 
making during the study.28,29,30 Patients with hyperglycemia, current gallstone disease, 
alcoholism, or other conditions in the investigator’s judgment would predispose the patient to 
pancreatitis will be excluded to this study. There have been no reports of pancreatitis in 
patients treated to date with PF-06463922. Elevations in lipase and amylase have been 
observed in some patients but not associated with either radiographic or symptomatic 
findings of pancreatitis. These parameters will continue to be regularly monitored in 
Phase 2. 

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Increased blood pressure (BP) and biphasic heart rate (HR) changes were observed in rats at 
a therapeutic index (TI) >2.6X and decreased BP and increase in HR in dogs at 
TI=6.2X, with no ECG change. Therefore, in this study, blood pressure and heart rate 
changes as vital signs will be monitored along with close monitoring for clinical 
cardiovascular parameters, such as changes in left ventricular ejection fraction (LVEF), ECG 
changes and potential cardiovascular symptoms. Changes in LVEF and QTc were observed 
in some Phase 1 patients, although few were considered to be adverse events; 2 patients had 
Grade 1 QTc prolongation that was considered treatment-related, and no patients had 
treatment-related changes in LVEF. Heart rate changes were also observed in Phase 1, but 
none were considered adverse events. PR interval prolongation has been observed in both 
healthy volunteer studies (Study B7461008) and clinical trials (Study B7461001). In the 
healthy volunteer Study B7461008, the PR interval prolongation was associated with 
1 episode of transient second-degree atrioventricular (AV) block (Mobitz type 1; 
Wenckebach). In the clinical Study B7461001, the PR interval prolongation may have been 
associated with the progression of pre-existing AV block to complete heart block. When the 
complete heart block was identified, the patient was immediately evaluated and subsequently 
treated by placement of an implanted pacemaker. In response to the observation of PR 
interval prolongation, data from all available human studies (approximately 100 patients in 
clinical studies and 45 in single dose healthy volunteer studies) was reviewed. Additional 
instances were identified of asymptomatic increases in the PR interval, usually most 
notable during Cmax (1-2 hours post-dose). Of note, the patients with a PR interval 
>200 msec were generally those with a baseline value at the upper end of the normal 
range. The ECG changes appear limited to the PR interval, with no impact on QRS or QT 
intervals. This impact on the PR interval is supported by preclinical animal studies, as 
described in the current IB. To further characterize the observed PR prolongation, a separate 
drug-drug interaction (DDI) and Holter monitoring study will be performed in a cohort of 
patients. 
Prompt medical intervention is recommended at the first sign of appearance of cutaneous 
toxicity including topical or oral corticosteroids if required according to investigator’s 
judgment. 
Regenerative anemia was observed in dogs at TI =24X and lymphoid hypocellularity in the 
spleen in rats TI=13X. In this study hematological parameters will be regularly monitored. 
Anemia was reported in some Phase 1 patients, although few cases were considered to be 
adverse events; 2 patients had Grade 2 treatment-related anemia and 1 patient had 
treatment-related Grade 3 anemia. Hematologic parameters will continue to be regularly 
monitored in Phase 2. 
As the potential for CNS effects and cognitive deficit were suggested from safety 
pharmacology and general toxicity studies, close clinical monitoring including a site staff 
directed questioning tool and a patient reported outcome measure with cognitive domains, 
will be performed for signs or symptoms of cognitive disturbance or neurotoxicity. Because 
various CNS effects were reported among the first 15 patients enrolled and treated with 
PF-06463922 in the Phase 1 portion of this clinical study, at least 12 patients in Phase 1 will 
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to better characterize these CNS effects. Additionally, the Phase 1 portion will be modified 
to additionally assess the impact of twice daily (BID) dosing and of food on 
PF-06463922 safety and PK. Treatment-related CNS effects were observed in 18 (36%) 
Phase 1 patients. In Phase 2, close monitoring for these effects will be performed by routine 
cognitive assessment, mood characterization, and suicidal ideation and behavior monitoring. 
Weickhardt et al31 recently reported decreases in total testosterone levels in 32 ALK+ 
NSCLC patients on crizotinib treatment. There were several limitations of this analysis, 
including but not limited to diurnal timing of the blood samples and insufficient baseline 
versus on-treatment total and free testosterone levels over time, and thus a further systematic 
assessment of testosterone levels to understand the validity of these data is warranted. 
However, and even if no preclinical safety signal was observed with PF-06463922, the study 
of hypogonadism laboratory assessments will be performed in this study to understand if 
these observed laboratory findings can be attributed to a ALK inhibitor class effect. 
Elevations in cholesterol (up to 2.2-fold) were observed in rat and dog studies. Therefore, in 
this study, cholesterol (a complete cholesterol panel) and triglycerides will be regularly 
monitored. Hypercholesterolemia was the most frequently occurring adverse event in 
Phase 1. Patients who have elevated cholesterol or triglyceride levels should receive 
concomitant treatment with a statin or other lipid-lowering agent at the first instance of 
elevation and then be closely monitored for any changes. Agents that should be considered 
are provided in Section 5.3.2.6. The choice and dosing of statins may be guided by 
information on the differential metabolism by the cytochrome P450 pathway. 
PF-06463922 has been shown to induce embryonic and fetal toxicity in animals. Patients 
who are pregnant and who are breastfeeding are excluded from the study. Additionally, male 
and female patients of childbearing potential and at risk for pregnancy must agree to use a 
highly effective method of contraception from the time of the first negative pregnancy test at 
screening, throughout the study, and for 97 days after the last dose of assigned treatment if 
male patients, 21 days if female patient. Male patients must agree to refrain from donating 
sperm throughout the study and for 97 days after the last dose of assigned treatment. 
1.3.6. PF-06463922 Pharmacokinetics in Animals and Projection of Human 
Pharmacokinetics 
The single-dose pharmacokinetics of PF-06463922 was evaluated in nonclinical species 
following intravenous (IV) and oral administration. Plasma clearance (CL) in rats and dogs 
were 16 mL/min/kg and 9 mL/min/kg, respectively. PF-06463922 was moderately to rapidly 
absorbed after a single oral dose to rats and dogs, with high oral bioavailability observed in 
both species (~100% rats; 97% dogs). Renal excretion of the parent drug was limited in rats 
and dogs. Systemic exposures (peak concentration [Cmax] and area under the 
concentration-time curve [AUC]) to PF-06463922 increased with increasing dose in an 
approximately proportional manner in the pivotal toxicology studies in rats (up to 
30 mg/kg/day) and dogs (up to 25 mg/kg/day). The binding of PF-06463922 to plasma 
proteins ranged from 64%, 71% and 66% for rat, dog, and human, respectively. 
PF-06463922 was detected in the brain and cerebrospinal fluid (CSF) after oral dosing to 
rats, indicating that PF-06463922 can cross the blood brain barrier. 

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In vitro and in vivo metabolite profiling suggested that the primary clearance mechanisms for 
PF-06463922 were by cytochrome P450 (CYP)- and uridine 
5’-diphosphoglucuronosyltransferase (UGT)-mediated oxidation and glucuronidation 
reactions, respectively. In vitro studies using human recombinant CYP and UGT enzymes 
suggested that CYP1A2, 2B6, 2C9, and 3A4 primarily mediated oxidative metabolism of 
PF-06463922, and UGT1A4 was the primary enzyme responsible for the glucuronidation. 
Comparison of hepatocyte metabolic profiles across nonclinical species and human suggested 
that human metabolism is substantially different from mouse, rat, and dog, with 3 unique 
metabolites to human in vitro preparations. PF-06463922 did not inhibit CYP1A2, 2B6, 
2C8, 2C19, or 2D6 enzymes (50% inhibitory concentration [IC50] >100 M) by either 
competitive or time-dependent inhibition. While CYP2C9 was inhibited by 
PF-06463922 with an IC50 value of 44 M, PF-06463922 was not a time-dependent 
inhibitor of CYP2C9. CYP3A4/5 activities were inhibited by PF-06463922, with 
IC50 values of 23, 10, and 22 M, measured as testosterone 6-hydroxylase, midazolam 
1´-hydroxylase, and nifedipine oxidase activities, respectively. Time-dependent inhibition 
was demonstrated for CYP3A4/5 by PF-06463922, with a shift in IC50 values (0.81, 0.74, 
and 0.87 M) after a 30 minute pre-incubation period. In in vitro studies using 3 lots of 
human hepatocytes, CYP2B6 and 3A4 activities and messenger Ribonucleic acid (mRNA) 
concentrations were induced by PF-06463922. Therefore, PF-06463922 can potentially alter 
the pharmacokinetics of other coadministered drugs that are eliminated by the CYP2B6 and 
3A4 pathways. 
The human pharmacokinetics of PF-06463922 were predicted using in vitro to in vivo 
scaling of human hepatocyte data and GastroPlus human physiological based 
pharmacokinetic modeling. Human CL, steady-state volume of distribution (Vss), half-life 
(t½), and oral bioavailability are predicted to be 3 mL/min/kg, 3 L/kg, 12 hours, and 86%, 
respectively. Using the pharmacodynamic parameters estimated from mouse xenograft 
studies and predicted human pharmacokinetic parameters, it is projected that twice daily 
(BID) doses of 10 mg of PF-06463922, corresponding to a steady-state average concentration 
(Cav,ss) of 51 nM (21 ng/mL) free or 150 nM (61 ng/mL) total, would be required to 
significantly inhibit ALK phosphorylation in patient tumors and achieve the expected 
significant antitumor efficacy. Safety margins were calculated using animal exposures 
relative to the projected human steady-state total exposure (Cmax 87 nM [35 ng/mL] free or 
256 nM [104 ng/mL] total; AUC 1228 nM•h [499 ng/mL] free or 3612 nM•h 
[1468 ng•h/mL] total) at the predicted human efficacious dose of 10 mg BID. 
For more details about the ADME of PF-06463922, refer to the Investigator’s Brochure 
(IB).22 
1.3.6.1. PF-06463922 Pharmacokinetics in Phase 1 
1.3.6.2. Study B7461001 
The B7461001 dose-escalation study evaluated pharmacokinetics (PK) in 34 and 37 patients 
for single- and multiple-dose PK, respectively. Doses ranged from 10-200 mg QD. Also 
evaluated was the effect on midazolam (as a probe for CYP3A4), fed/fast conditions, and 
BID regimens, using the acetate solvate solid oral tablet formulation. 

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Preliminary single-dose PK of PF-06463922 under fasted conditions indicated peak plasma 
concentrations (Cmax) of PF-06463922 were achieved at median time (Tmax) ranging from 
1.0-2.0 hours. Mean Cmax and AUCinf values for PF-06463922 ranged from 50.8 to 
1201 ng/mL and from 900 to 21429 ng•hr/mL, respectively, and increased in a relatively 
dose-proportionate manner. Mean estimates of terminal half-life ranged from 16.3 to 
27.4 hours. 
After multiple once daily doses of PF-06463922 in the fasted state of PF-06463922 were 
achieved at median time (Tmax) ranging from 1.0-2.0 hours. Mean Cmax and AUCτ values for 
PF-06463922 ranged from 67.3 to 1043 ng/mL and from 713 to 8057 ng•hr/mL, respectively. 
At doses greater than 50 mg QD, steady state AUC values increased in a less than 
dose-proportional manner. Mean estimates of effective half-life ranged from 11.8 to 
23.4 hours. At 75 mg and 100 mg QD for 15 days, the accumulation indices were 0.52 and 
0.61 of those predicted, respectively. 
In vitro data indicated that PF-06463922 had time-dependent inhibition of CYP3A4/5. The 
CYP3A4/5 substrate drug midazolam was given with and without 25 mg and 150 mg 
PF-06463922 to a total of 6 patients (see Section 1.3.9). Preliminarily, the AUCinf and Cmax 
geometric mean (CV%) were reduced about 48 and 63% and 24 and 18% in the presence of 
daily PF-06463922 at either 25 mg or 150 mg, respectively, due to PF-06463922 inducing 
CYP3A4/5. Concomitant use of PF-06463922 with medications which are 
CYP3A4/5 substrates has potential to reduce the concentration of sensitive CYP 
3A4/5 substrates and caution is advised when co-administering with PF-06463922. 
PF-06463922 100 mg single-dose acetate solvate solid oral tablet formulation was given after 
an overnight fast or after a high-fat, high-calorie breakfast. Preliminary data from 5 patients 
indicated that the geometric mean Cmax and AUC were centered around 1 with a wide 90% 
confidence interval (CI), which did not allow establishment of any significant differences 
between fed and fast conditions based on the available data. Tmax values were shifted to the 
right in presence of food, with similar Cmax values. The range of data for the fed condition 
was entirely contained within the range of the fasted condition suggesting no significant 
difference between fed and fasted conditions. 
Three dose levels were given BID: 35 mg, 75 mg, and 100 mg. All 3 dose levels had 
steady-state AUC less than the steady-state AUC from the corresponding dose given QD. 
Administering PF-06463922 BID was not pursued due to the limited information available 
from these patients and the lack of tolerability, especially at 100 mg BID. 
1.3.6.3. Relative Bioavailability Study B7461005 
This study (B7461005) was a Phase 1, randomized (3 Period, 6 Sequence, Crossover), 
open-label study in 19 healthy volunteers to estimate the bioavailability of 2 new 
PF-06463922 formulations (using free base and maleate forms of API) relative to acetate 
solvate reference formulation (given in Phase 1 part of Study B7461001) given under fasted 
conditions. These new formulations were evaluated to identify options for improved drug 
product stability over the acetate formulation. 

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The results of the B7461005 bioavailability study indicated that the free base AUCinf ratio to 
acetate solvate reference was contained within the 90% CI and met the bioequivalence 
criterion of 80 to 125%. The Cmax for the free base formulation was decreased by 15% and 
the 90% CI did not include 100%, and the lower bound was less than 80%. However, no 
starting dose adjustment would be needed between free base and acetate formulations based 
on similar AUC results. 
While the results for the maleate versus acetate reference were similar for AUCinf and 
Cmax, the free base formulation provides optimum drug product stability and was therefore 
selected for use in the Phase 2 part of Study B7461001. 
1.3.7. Rationale for Selection of the Starting Dose in Phase 1 
The starting dose for PF-06463922 in the first-in-patient trial in cancer patients has been 
determined to be 10 mg daily, based on information derived from the 1-month repeat dose 
toxicology studies in rats and dogs. 
According to DeGeorge et al,10 the currently accepted algorithm for calculating a starting 
dose in clinical trials for cytotoxic agents is to use one-tenth of the dose that causes severe 
toxicity (or death) in 10% of the rodents (STD10, severely toxic dose) on a mg/m2 basis, 
provided this starting dose does not cause serious, irreversible toxicity in a non-rodent 
species. If irreversible toxicities are produced at the proposed starting dose in non-rodents or 
if the non-rodent is known to be the more appropriate animal model, then the starting dose 
would generally be one-sixth of the highest dose tested in the non-rodent that does not cause 
severe, irreversible toxicity (HNSTD, highest non severely toxic dose). The doses tested in 
the 1-month toxicology study in the male/female rats were 2/1, 8/4, and 30/15 mg/kg/day 
orally, and in the 1-month dog study were 2, 7, and 25 mg/kg/day orally. The STD10 in 
male/female rats was determined to be 8/15 mg/kg/day respectively (free 
AUC24 5760/24660 ng.h/mL) and HNSTD following 1 month of dosing was 25 mg/kg/day in 
dogs (free AUC24 40000 ng•h/mL). 
The human equivalent starting dose was calculated to be 8.6 mg based on the rat STD10 of 
8 mg/kg/day, and 150 mg based on the HNSTD of 25 mg/kg/day in the dog (assuming a body 
surface area of 1.8 m2 for humans). Because the rat was determined to be the more sensitive 
species and provides a lower starting dose, the dose of PF-06463922 will be rounded to 
10 mg and used as the starting dose for the FIP study. At the starting dose of 10 mg dose 
once daily, the projected unbound exposure (AUC24, 249 ng/ml) is ~23-fold lower than the 
unbound exposure observed (AUC24, 5760 ng/ml) at rat STD10 dose and provides a good 
safety margin. 
1.3.8. Rationale for Recommended Phase 2 Starting Dose 
Although the adverse event profile of PF-06463922 in Phase 1 consists mostly of laboratory 
abnormalities, none of which were dose limiting, there was concern over the appearance of 
CNS effects particularly at those doses higher than 100 mg QD. Although the CRM model 
recommended dose escalation above 200 mg QD, the CNS effects observed at this dose and 
at the 150 mg QD dose were considered intolerable to some patients and were a cause for 
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upon by the sponsor and the Phase 1 investigators to test and re-test doses lower than 200 mg 
QD and consider an alternative dosing regimen. 
BID dosing was employed to potentially modulate these adverse events, but the patients in 
BID cohorts had limited time on therapy (75 mg BID and 100 mg BID) and did not tolerate 
100 mg BID well. 
Overall, 100 mg QD was a well-tolerated dose. None of the patients at this dose required 
dose reduction. Dose delays did occur in 29% of patients, but these dose delays were not 
attributed to CNS effects, but rather to hypercholesterolemia or hypertriglyceridemia, or to 
disease-related events. 
Additionally, based on the PK data observed, simulated patient exposure suggested that the 
100 mg QD dose was the lowest dose that would exceed the PF-06463922 Ceff of 150 ng/mL 
during the majority of the dosing cycle once steady-state was reached. The Ceff of 
150 ng/mL was a concentration predicted to result in ˃80% tumor growth inhibition of the 
ALK G1202R resistance mutation. Further, PF-06463922 demonstrated response rates of 
37% (including a 30% intracranial response rate), which indicated that this compound is 
active both inside and outside the brain. 
Taken together, the 100 mg QD dose was chosen as the RP2D based on the entirety of the 
safety, efficacy, and clinical pharmacology data. 
1.3.9. Rationale for Evaluation of Midazolam (MDZ) Interaction 
PF-06463922 showed time-dependent inhibition of CYP3A isozymes in human liver 
microsomes with a kinact and KI of 0.218 min-1 and 2.81 M, respectively, and inactivation 
efficiency (kinact/KI) of 77.6 min-1 *M-1. CYP3A induction was also observed in human 
hepatocytes. Preliminary SimCYP simulations were performed to assess the net effect of 
steady-state PK of PF-06463922 on the metabolic activity of midazolam (2 mg). At 
projected human efficacious dose of 20 mg once daily (or 10 mg BID), the ratios of AUC and 
Cmax of midazolam with and without PF-06463922 were 12 and 3, respectively, suggesting a 
net effect of inhibition. There is a potential for more potent inhibition in patients receiving 
higher doses, leading to substantial drug interactions with commonly coadministered drugs 
that are CYP3A substrates. In addition, PF-06463922 may display nonlinear 
pharmacokinetics in patients that may require dose adjustments. To mitigate these risks, a 
MDZ interaction sub-study has been built into this First in Patient (FIP) study to assess the 
potential PF-026463922 related CYP3A inhibition/induction. 
MDZ is a benzodiazepine used clinically for conscious sedation. It undergoes extensive 
metabolism via CYP3A4/5 and is a widely accepted in-vivo probe for assessing CYP3A 
activity. In the current trial, midazolam PK following a single oral 2-mg dose will be 
evaluated before and after repeated daily administration of PF-06463922 at 3-4 dose levels 
(fewer dose levels may be evaluated depending on emerging PK results), in order to assess 
the effects of PF-066463922 on CYP3A activity in the gastro-intestinal tract and the liver. 
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determine if there is any need for concomitant medication restrictions or dose modifications 
in future studies. 
1.3.10. Rationale for Crizotinib Treatment after PF-06463922 Resistance 
Crizotinib was the first approved ALK inhibitor for advanced ALK+ NSCLC patients, and 
since that time, much has been learned about its anti-tumor activity as well as the subsequent 
development of acquired resistance. In contrast, less is known about the development of 
resistance to the second-generation ALK inhibitors, alectinib and ceritinib; even less is 
known about the development of resistance to PF-06463922. However, certain key 
principles have emerged which shape the current understanding and support the use of 
crizotinib after failure of PF-06463922 in ALK+ NSCLC patients who were treatment naive 
prior to receiving PF-06463922. 
Resistance has been characterized as either ALK-independent (eg, bypass track activation) or 
ALK-dependent (eg, gene amplification or ALK mutation). 
The bypass tracks for crizotinib have been noted to be EGFR, KIT, SRC, and IGF-1R.45 In 
considering activation of other oncogenic drivers in response to treatment with 
second-generation ALK inhibitors, it is important to note that crizotinib inhibits tyrosine 
kinase c-MET (MET) whereas alectinib and ceritinib do not. Notably, MET has been 
described as a mechanism of resistance to alectinib in preclinical work selecting for alectinib 
resistance in cell lines and has been described in clinical experience with alectinib.46,47,48 As 
a MET inhibitor, crizotinib was effective at inhibition of cell growth in vitro of 
alectinib-resistant cells lines and was effective in treating the alectinib-resistant patient 
reported by Gouji and colleagues. Because PF-06463922 is not an inhibitor of MET, it is 
plausible that MET induction is also a potential mechanism of resistance to PF-06463922. 
An additional line of evidence supports the use of crizotinib after PF-06463922. In the 
Phase 1 portion of this trial, a patient whose disease progressed on PF-06463922 was 
subsequently treated with crizotinib off study and had a second response; the mechanism of 
this activity may be the result of a new mutation which conferred sensitivity to crizotinib but 
resistance to study drug. 
Thus, treatment with crizotinib after the emergence of resistance to PF-06463922 is 
reasonable and worth exploring in a population of patients who were treatment naïve prior to 
receiving PF-06463922. 
1.3.11. Rationale for Drug-drug Interaction and Holter Monitoring 
In vitro studies in human hepatocytes indicate that PF-06463922 may induce the metabolic 
enzyme CYP2B6 that could in turn lead to decreased exposure of drugs that are metabolized 
by CYP2B6. In addition, the in vitro observation that PF-06463922 also induces the 
metabolic enzyme CYP3A was confirmed clinically in a DDI evaluation with midazolam in 
the Phase I portion of this study. 

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The nuclear receptor PXR (pregnane X receptor) is widely accepted as the principal 
transcriptional regulator of CYP3A induction by xenobiotics. Activation of PXR is 
hypothesized to induce various other drug metabolizing enzymes, such as CYP2C8, 
CYP2C9, and CYP2C19, selected isoforms of UGTs, and efflux proteins such as P-gp. 
Further, In vitro data also indicates that PF-06463922 is a time-dependent inhibitor of 
CYP3A, and also inhibits CYP2C9, UGT1A1, UGT2B7 and P-gp. 
Complex interactions, such as induction or net effect of induction along with inhibition of a 
specific enzyme or efflux transporter, can only be adequately evaluated following continuous 
multiple dosing of the perpetrator drug and using selective probes for the enzyme/transporter 
being investigated. The potential of PF-06463922 to induce key CYP enzymes and P-gp 
following multiple dosing of PF-06463922 will be evaluated in subjects enrolled in this 
cohort using selective probes substrates. 
Additionally, as detailed in Section 1.3.5, PR interval prolongation has been observed in both 
healthy volunteer studies (Study B7461008) and the ongoing B7461001 study. To 
characterize the effects of PF-06463922 on ECG endpoints, continuous Holter telemetry of 
patients enrolled in this substudy will be used to evaluate the effect of PF-06463922 on the 
PR interval by comparing the patient’s pre-drug baseline with PR interval observations 
associated with exposure of PF-06463922 following a single dose and at steady state. 
In order to ensure patients have had exposure to prior treatments, this study will only be 
conducted in patients who meet the prior treatment requirements of EXP groups 2-6, as 
defined in Section 3.1. 
Complete information for PF-06463922 may be found in the Single Reference Study 
Document (SRSD), which for this study is the Investigator’s Brochure.22 
Complete information for crizotinib (as applicable) may be found in the Investigator’s 
Brochure.42 
2. STUDY OBJECTIVES AND ENDPOINTS 
2.1. Objectives 
This study has separate primary and secondary objectives for the Phase 1 and 
Phase 2 study portions. 
Phase 1 Portion of the Study 
Primary Objective: 
• To assess safety and tolerability of PF-06463922 as a single agent at increasing dose 
levels in patients with advanced ALK+ or advanced ROS1+ NSCLC in order to 
estimate the Maximum Tolerated Dose (MTD) and select the Recommended 
Phase 2 Dose (RP2D). 
Secondary Objectives: 
• To evaluate the overall safety and tolerability of PF-06463922. 

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• To evaluate the single- and multiple-dose PK profiles of single-agent PF-06463922. 
• To detect early signs of cognitive dysfunction. 
• To evaluate patient reported outcomes (PRO) of global Quality of Life (QOL) 
functioning, and the impact of PF-06463922 on disease/treatment-related symptoms 
of lung cancer. 
• To evaluate the potential of single-agent PF-06463922 to cause CYP3A 
inhibition/induction using midazolam as a probe. 
• To characterize the effects of single-agent PF-06463922 on the QTc interval. 
• To evaluate tumor and blood-based molecular markers of response and resistance to 
single-agent PF-06463922. 
• To characterize the effect of food on PF-06463922. 
• To evaluate preliminary anti-tumor activity of single-agent PF-06463922 in patients 
with advanced ALK+ NSCLC or advanced ROS1+ NSCLC. 
• To evaluate response to prior systemic therapies. 
Exploratory Objectives: 
• To explore the brain penetration of single-agent PF-06463922. 
Phase 2 Portion of the Study 
Primary Objective: 
• To evaluate overall (intra- and extra-cranial) and intracranial anti-tumor activity of 
single-agent PF-06463922 at RP2D in patients with advanced ALK+ NSCLC and 
advanced ROS1+ NSCLC. 
Secondary Objectives: 
• To confirm the safety and tolerability of single-agent PF-06463922 at the RP2D. 
• To confirm single- and multiple-dose PK profiles of single-agent PF-06463922 at the 
RP2D. 
• To assess secondary measures of clinical efficacy. 
• To detect early signs of changes in mood, cognitive function, or suicidal ideation and 
behavior (SIB). 

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• To evaluate patient reported outcomes (PRO) of global QOL, functioning and the 
impact of PF-06463922 on disease/treatment-related symptoms of lung cancer at the 
RP2D. 
• To further evaluate the effects of single-agent PF-06463922 at the RP2D on the QTc 
interval. 
• To further evaluate tumor and blood-based molecular markers of response and 
resistance to single-agent PF-06463922 at the RP2D. 
• To evaluate the safety and efficacy of single-agent crizotinib following 
PF-06463922 in treatment-naïve patients with advanced ALK+ NSCLC. 
• To evaluate response to prior systemic therapies. 
Exploratory Objectives: 
• To explore the brain penetration of single-agent PF-06463922 at the RP2D. 
Japanese Patient Only Lead-In Cohort (LIC) 
• To evaluate the safety and tolerability of PF-06463922 in Japanese Patients before 
starting enrollment of Japanese Patients in phase 2 portion of the study. 
Drug-Drug Interaction (DDI)/Holter Monitoring Study 
• To evaluate the potential of PF-06463922 to inhibit/induce CYP2B6, CYP2C9, P-gp, 
and select UGT isoforms. 
• To characterize the effects of PF-06463922 on ECG endpoints. 
• To characterize the safety and efficacy of PF-06463922 of patients entering the 
DDI/Holter monitoring study. 
2.2. Endpoints [Please ensure endpoints changes remain aligned with Section 9.] 
Phase 1 Primary Endpoint: 
• Cycle 1 Dose-Limiting Toxicities (DLTs). 
Phase 2 Primary Endpoint: 
• 
Objective tumor response, as assessed by Response Evaluation Criteria in Solid 
Tumor (RECIST) version 1.1 (Appendix 3). In patients with asymptomatic CNS 
metastases, up to five (5) intracranial target lesions in addition to the five (5) 
extracranial target lesions will be assessed.32 

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Secondary Endpoints [all patients unless otherwise indicated]: 
• Adverse Events as characterized by type, frequency, severity (as graded by NCI 
CTCAE v.4.03), seriousness and relationship to study therapy. 
• Laboratory abnormalities as characterized by type, frequency and severity (as graded 
by NCI CTCAE v.4.03). 
• Left Ventricular Ejection Fraction (LVEF). 
• Vital Signs (heart rate, blood pressure). 
• Total Mini-Mental State Examination Score [Phase 1 only]. 
• Mood assessment, Cognitive Function assessment, Suicidal Ideation and Behavior 
assessment [Phase 2 only]. 
• Pharmacokinetic parameters of PF-06463922: Single Dose - Cmax, Tmax, AUClast, 
AUC, CL/F, and Vz/F and t1/2, AUCinf as data permit. Multiple Dose (assuming 
steady-state is achieved) - Css,max, Tss,max, AUCss,, t1/2, Css,min, Css,av, CL/F, Vz/F, Rac 
(AUCss,/AUCsd,) and Rss (AUCss,/AUCsd,inf) as data permit. Phase 1 only: urine PK 
parameters (Ae%, and CLR) of PF-06463922 from MDZ and food effect substudy. 
• Phase 1 only: pharmacokinetic parameters of midazolam: Cmax, Tmax, AUClast, CL/F, 
and Vz/F and t1/2, AUCinf as data permit. 
• Patient reported functioning and impact on disease/treatment-related symptoms of 
lung cancer and global QOL. 
• QTc interval. 
• Disease Control Rate (DCR) at 12 and 24 weeks defined as the percent of patients 
with a confirmed complete response (CR), partial response (PR) or stable disease 
(SD) according to RECIST 1.1 at 12 and 24 weeks. 
• 
Objective tumor response, as assessed by Response Evaluation Criteria in Solid 
Tumor (RECIST) version 1.1 (Appendix 3) [Phase 1 only – primary endpoint in 
Phase 2]. In patients with asymptomatic CNS metastases, up to 5 intracranial target 
lesions in addition to the 5 extracranial target lesions will be assessed.32 
• Time-to-event endpoints: Progression-Free Survival (PFS), Overall Survival (OS), 
Duration of Response (DR), and Time to Tumor Response (TTR). 
• Probability of first event being a CNS progression, non CNS progression, or death. 
• Time to Progression (TTP) [Phase 2 only]. 
• Response to prior systemic therapies. 

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• Selected molecular profiling of tumor tissue, eg, ALK kinase domain mutations and 
circulating nucleic acid (CNA), eg, ALK kinase domain mutations. 
Secondary Endpoints [ALK+ NSCLC Phase 2 patients receiving single-agent crizotinib 
following first-line treatment with PF-06463922]: 
• Adverse Events as characterized by type, frequency, severity (as graded by NCI 
CTCAE v.4.03), seriousness and relationship to study therapy. 
• Laboratory abnormalities as characterized by type, frequency, and severity (as graded 
by NCI CTCAE v.4.03). 
• Objective tumor response, as assessed by Response Evaluation Criteria in Solid 
Tumor (RECIST) version 1.1, and time-to-event endpoints including PFS, DR, TTR 
and OS. 
Phase 1 Exploratory Endpoints: 
• Time to Progression (TTP). 
Phase 1 and 2 Exploratory Endpoints: 
• CSF concentration of PF-06463922. 
Japanese Patient Only Lead-In Cohort (LIC) 
• Cycle 1 Dose Limiting Toxicities (DLTs). 
Endpoint for Drug-Drug Interaction (DDI)/Holter Monitoring Study 
• Pharmacokinetic parameters (as data permit) for probe substrate after single oral 
administration with or without PF-06463922: Plasma AUC24, AUClast, AUCinf, Cmax, 
Tmax, CL/F, Vz/F and t1/2. 
• Pharmacokinetic parameters (as data permit) for relevant probe substrate 
metabolite(s) and PF-06463922 metabolite(s): Plasma and AUC24, AUClast, AUCinf, 
Cmax, Tmax, t1/2, MRCmax, MRAUCinf, and MRAUClast. 
• PR interval with PF-06463922 treatment. 
3. STUDY DESIGN 
3.1. Study Overview 
This is a Phase 1/2, open-label, multicenter, multiple-dose, dose-escalation, safety, PK, PD 
and anti-cancer efficacy exploration study of PF-06463922 as a single agent in patients with 
advanced ALK+ or advanced ROS1+ NSCLC. This clinical study will consist of 2 parts, 
Phase 1 and Phase 2. 

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Figure 1. Study Schema 
Phase 1: 
* Treatment until PD or unacceptable toxicity. 
Phase 2: 
 
 
 
 
 
 
 
 
 
 
 
• Asymptomatic brain metastases allowed in all cohorts. 
• Preplanned analysis for Phase 2 ALK+ NSCLC patients with brain metastases. 
* Treatment until PD or unacceptable toxicity. 
# Prior 2 or 3 TKIs refers to line of therapy. For example, if the same TKI were given 
twice, that would be considered as 2 prior lines of treatment. Any number of lines of 
prior chemotherapy are allowed. 
The Phase 1 portion of the study will estimate the MTD for single-agent PF-06463922 in 
dose escalation cohorts in patients with advanced ALK+ or advanced ROS1+ NSCLC with 
or without asymptomatic CNS metastases, and will enroll approximately 36 patients 
(depending on toxicities observed). Additional patients (approximately 15) beyond 36 may 
be enrolled to better characterize RP2D, which could include safety, PK, alternative dosing 
schedules (if applicable), food effect, etc. 
To understand the single-dose pharmacokinetics (PK) of PF-06463922, a lead-in period 
preceding the continuous daily dosing will be conducted. A single lead-in dose of 
PF-06463922 will be given on Day -7. No trial drug will be administered during the interval 
between the lead-in single dose and Day 1 of the first cycle. The lead-in period and 
ALK/ROS+ NSCLC: 
Treatment-naïve in advanced setting or PD 
after prior ALK TKI; any prior chemo 
Dose escalation: DL1 = 10 mg 
CRM design: 25 mg – 400 mg 
PF-06463922 
once daily or BID* 
EXP-1 ALK Treatment Naive 
EXP-6 ROS1 any line 
EXP-3 ALK prior Crizo or other 
TKI + 1-2 Chemotherapy 
# 
EXP-5 ALK 3 prior TKIs 
EXP-2 ALK prior Crizo only 
PF-06463922 
100 mg QD* 
# 
EXP-4 ALK 2 prior TKIs 

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subsequent doses timing, dosing regimen, and PK time points may be modified based on the 
emerging PK data. 
To evaluate the effect of PF-06463922 on CYP3A inhibition/induction, a midazolam (MDZ) 
drug-drug interaction (DDI) substudy will be conducted at 3 to 4 PF-06463922 dose levels 
(fewer dose levels may be evaluated depending on emerging PK results) in Phase 1. Patients 
enrolled in the MDZ interaction sub-study will receive a single 2 mg oral dose of MDZ on 
Day –7. These patients will receive another single 2-mg oral dose of MDZ concurrently with 
PF-06463922 on Cycle 1 Day 15 (morning dose if BID schedule). During the study, 
real-time pharmacokinetic monitoring will be conducted as much as possible. Additionally, a 
food effect substudy will be conducted in approximately 6 Phase 1 patients to gain 
preliminary information about the effects of food on PF-06463922 PK. 
On Cycle 1 Day 15, MDZ will be given concurrently with PF-06463922. Patients 
participating in the MDZ substudy will NOT receive any lead-in dose of PF-06463922 on 
Day -7. 
The Phase 2 portion of the study will be with single-agent PF-06463922 at the identified 
MTD/RP2D and will enroll patients with advanced ALK+ NSCLC and patients with 
advanced ROS1+ NSCLC, with or without asymptomatic CNS metastases. The Phase 2 will 
evaluate the anti-cancer activity of single-agent PF-06463922 in multiple subpopulations of 
patients with advanced ALK+ NSCLC and patients with advanced ROS1+ NSCLC and will 
allow to better define the safety, PK and pharmacodynamic profiles of single-agent 
PF-06463922 at the RP2D. Additionally, at the discretion of the treating investigator and if 
clinically indicated, patients who are ALK inhibitor treatment naïve at baseline (ie, part of 
EXP-1 subpopulation) and who discontinue PF-06463922 due to reasons other than 
withdrawal of consent may be eligible to receive single-agent crizotinib. At the time of 
PF-06463922 discontinuation, patients who are eligible to receive crizotinib will undergo a 
brief Screening period to ensure inclusion and exclusion criteria are met and required 
assessments are performed (see Appendix 11). 
To evaluate the safety and tolerability of PF-06463922 in Japanese patients, a Japanese 
patient only lead-in cohort (LIC) will be enrolled to evaluate PF-06463922 safety and PK in 
Japanese patients treated at a previously tested dose in Phase 1. The LIC will be conducted 
at Japanese sites concurrently with the Phase 2 portion of the study but will be considered 
separate from Phase 2 enrollment. A minimum of 3 Japanese patients will be enrolled into 
the LIC. Japan will participate in Phase 2 after completion (DLT evaluation) of LIC. 
Patients enrolled into the LIC will follow the same eligibility criteria, study procedures 
(unless otherwise specified), and patient withdrawal criteria as outlined in Phase 2. The 
PF-06463922 starting dose for the LIC will be communicated by letters to the investigators 
after identification of the RP2D in Phase 1. Following 1 cycle of dosing, a safety review will 
be performed. If, based on the safety profile in the first cycle of treatment, PF-06463922 is 
shown to be tolerable in Japanese patients, then Japan sites will join the Phase 2 portion of 
the study. The required assessments and safety review process for the Japanese patient only 
LIC are outlined in Appendix 9 and Appendix 10, respectively. 

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To evaluate the potential interaction of PF-06463922 on drugs that are metabolized or 
transported via pathways that include CYP2B6, CYP2C9, P-gp, and select UGT isoforms, a 
drug-drug interaction (DDI) study will be conducted in approximately 30 (6 evaluable for 
each probe substrate) patients who meet the prior treatment requirements of EXP groups 2-6. 
Additionally, within this study, an evaluation of the effects of PF-06463922 on the PR 
interval will be conducted via continuous Holter telemetry comparing the subject’s 
time-matched PR interval (approximately 10 points) with exposure of 
PF-06463922 following a single dose and again at steady state. In addition, arrhythmia 
analysis will be performed in these patients and these data will be analyzed separately from 
Phase 2 data. This study will be conducted in approximately 10 participating Phase 2 sites 
and will begin and conclude upon official notification by the sponsor via letter or email. 
The Phase 2 will enroll approximately 260 patients and will include patients from the 
following subpopulations: 
• EXP-1: Treatment-naïve patients with advanced ALK+ NSCLC with or without 
asymptomatic CNS metastases. (targeting 30 patients). No prior chemotherapy is 
allowed in the metastatic setting. In those countries where standard of care does not 
allow for treatment-naïve ALK+ NSCLC patients to receive PF-06463922 in the 
first-line treatment setting, patients will not be enrolled into EXP-1 subgroup. 
EXP-1 patients may be eligible to receive single-agent crizotinib following treatment 
with PF-06463922 if allowed per local guidelines and appropriate per investigator 
discretion. 
• EXP-2: Patients with advanced ALK+ NSCLC with or without asymptomatic CNS 
metastases relapsing after only crizotinib therapy. (Targeting 80 patients between 
EXP-2 and EXP-3A-EXP-3B combined). No prior chemotherapy is allowed in the 
metastatic setting. 
• EXP-3: Patients with advanced ALK+ NSCLC with or without asymptomatic CNS 
metastases relapsing after crizotinib therapy and 1 or 2 prior regimens of 
chemotherapy given before or after crizotinib therapy [EXP-3A] OR patients with 
advanced ALK+ NSCLC with or without asymptomatic CNS metastases relapsing 
after 1 ALK inhibitor therapy other than crizotinib with or without any number of 
prior chemotherapy regimens in any disease setting [EXP-3B] (as above, targeting 
80 patients between EXP-2 and EXP-3A -EXP-3B combined). 
• EXP-4: Patients with advanced ALK+ NSCLC with or without asymptomatic CNS 
metastases relapsing after 2 prior lines of ALK inhibitor therapies (targeting 
70 patients). Patients may have had any number of prior chemotherapy regimens in 
any disease setting. 
• EXP-5: Patients with advanced ALK+ NSCLC with or without asymptomatic CNS 
metastases relapsing after 3 prior lines of ALK inhibitor therapies (targeting 
40 patients). Patients may have had any number of prior chemotherapy regimens in 
any disease setting. 

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• EXP-6: Patients with advanced ROS1+ NSCLC who are treatment naïve or have had 
any number of prior cancer therapies (targeting approximately 40 patients). Patients 
may or may not have asymptomatic CNS metastases. In those countries where 
standard of care does not allow for treatment-naïve ROS1+ NSCLC patients to 
receive PF-06463922 in the first-line treatment setting, patients will not be enrolled 
into EXP-6 treatment-naïve subgroup. 
Approximately 340 patients (Phase 1, Phase 2, and DDI and Holter monitoring study) are 
expected to be enrolled in the study overall. 
After the collection of data for the evaluation of primary objective is completed, and most of 
the secondary endpoints characterized, data recording will be limited to adverse events, with 
the purpose of performing long term safety assessments and overall survival. At the end of 
treatment the biological samples will be collected for translational analysis. 
Guidance on the management of patients on study is provided to investigators in Table 1. 
The revised schedule of activities will allow the investigators to perform most study tests and 
procedures per standard of care or clinical judgement. 
In all study parts, PF-06463922 will be administered orally once daily (QD) (or twice daily 
[BID] dosing in Phase 1) continuously in 21-day cycles. When BID dosing is used, the 
choice of BID dose levels will be evaluated based on emerging safety and PK data. Patients 
will self-administer PF-06463922 in the outpatient setting. On the days of PK sample 
collections, PF-06463922 will be administered in the clinic. The PF-06463922 starting dose 
in Phase 1 will be 10 mg. 
For each dose level in Phase 1, patients will be enrolled in cohorts of minimum 3 patients 
(unless 2 DLTs are observed in the first 2 patients tested at that dose level). If toxicity is 
observed at the first dose level, then a lower dose level (Dose Level -1) may be tested. 
Safety assessments (laboratory, instrumental and clinical) will be regularly performed to 
assess the safety profile of PF-06463922 as a single agent. 
Tumor assessments by computerized tomography/magnetic resonance imaging (CT/MRI) 
scans of Chest Abdomen Pelvis [CAP] and MRI of the brain will be performed at baseline, 
and the brain MRI and CAP will be repeated every 6 weeks 1 week on study for the first 
18 months in Phase 1 and first 30 months in Phase 2, and then every 12 weeks ±1 week 
beyond regardless of tumor involvement. Bone scans (or bone MRI if preferred by 
investigator) will be performed at baseline for all patients (regardless of bone involvement) 
and repeated every 12 weeks on study, only if evidence of bone metastases are observed at 
baseline. For patients with bone involvement at Screening, CT or MRI or other appropriate 
imaging for bone assessment will be done every 6 weeks 1 week up to 18 months in 
Phase 1 and up to 30 months in Phase 2, and every 12 weeks ±1 week thereafter (in addition 
to the every 12 week bone scan or bone MRI for detection of new disease) and responses will 
be confirmed 4 weeks later (RECIST v1.1) until documented progression of disease. For all 
tumor assessments, the method of assessment used at baseline should be the same method 

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used throughout the study. For patients who have documented disease progression, but are 
still receiving PF-06463922, tumor assessments are to be done according to local institutional 
standard of care. Tumor response will be assessed by the RECIST v1.1 (Appendix 3) with 
modification to account for intracranial tumor response as described below. 
For those patients entering the study with asymptomatic CNS metastases, the response of 
measurable intracranial disease (ie, lesions 5 mm) will be assessed by a modified version of 
RECIST v1.1.32 The RECIST v1.1 will be extended to include up to 5 intracranial target 
lesions and up to 5 extracranial target lesions. Intracranial target lesions must be between 
5 mm and 40 mm in diameter. Intracranial disease assessment may only be by 
gadolinium-enhanced MRI with MRI contingent slices of 1 mm for assessment of CNS 
metastases 5 mm but less than 10 mm. CNS lesions 10 mm will be assessed with 
gadolidium- enhanced MRI with MRI contingent slices of 5 mm. All other CNS lesions 
considered non measurable under these conditions will still be assessed by gadolidium MRI 
with contingent slices of 1 mm but will be reported as Non Target. 
Patients who have asymptomatic radiologically suspected leptomeningeal disease (LM) or 
carcinomatous meningitis (CM) and have negative cerebrospinal fluid (CSF) cytology may 
be eligible for Phase 1. In addition, in the Phase 2, patients who have leptomeningeal disease 
(LM) or carcinomatous meningitis (CM) will be eligible if the LM/CM is visualized on MRI 
or if documented baseline cerebral spinal fluid (CSF) positive cytology is available. These 
will be considered Non Target lesions. 
All radiologic images must be available for independent central radiology review as 
determined by the sponsor. Instructions for submission of these images will be provided in 
the Study Reference Manual. The independent central radiology review will be stopped 
when the data collection required for the primary and secondary endpoints is deemed 
sufficient. 
Upon approval of Amendment 8, the radiologic assessments will be performed according to 
local practice. 
Biomarker studies on tumor tissue and blood will be carried out to help understand the 
mechanism of action of PF-06463922, as well as potential mechanisms of resistance. Such 
results may help in the future development of PF-06463922. These analyses may also result 
in the identification of potential biomarkers of response to PF-06463922, ultimately leading 
to development of a patient selection strategy for further clinical investigation. 
In all study parts, patients will continue with the study treatment until progression of disease 
as determined by the investigator, unacceptable toxicity, death or consent withdrawal. 
Patients may continue PF-06463922 (or crizotinib, if administered after 
PF-06463922) treatment after objective progression of disease is determined if the patient is 
continuing to experience clinical benefit, in the opinion of the investigator, and after 
discussion with the Sponsor. 

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3.2. Japanese Patient Lead-In Cohort (Japan Sites Only) 
To date, there is no documented experience with PF-06463922 in Japanese patients. 
Therefore, to evaluate the safety and tolerability of PF-06463922 in Japanese patients, this 
study will include a Japanese patient lead-in cohort (LIC) to evaluate PF-06463922 safety 
and PK of in Japanese patients treated at a previously tested dose in Phase 1. The LIC will 
be conducted at Japanese sites concurrently with the Phase 2 portion of the study but will be 
considered separate from Phase 2 enrollment. Japan will participate in Phase 2 after 
completion (DLT evaluation) of LIC. Patients enrolled into the LIC will follow the same 
eligibility criteria, study procedures (unless otherwise specified), and patient withdrawal 
criteria as outlined in Phase 2. Initially up to 3 patients will be enrolled and treated. If a 
DLT is observed in 1 of the initial 3 treated patients, then 3 additional patients will be 
enrolled and treated. Patients who discontinue treatment before completing Cycle 1 (ie, the 
DLT observation period) or receive less than 16 of the planned 21 PF--06463922 doses for 
reasons other than treatment-related toxicity (eg, missed appointments, misplaced study drug 
supplies, development of coexisting medical condition rendering the patient unable to 
swallow medication, development of rapidly progressing disease) will be replaced for DLT 
evaluation but will remain in the overall safety and efficacy analyses. If 33% patients 
experience DLT (0/3 or 1/6), then the tested dose would be considered tolerable in Japanese 
patients, and the Phase 2 portion of the study will be opened to Japan sites. If >33% patients 
experience DLT, then Japan sites will not join the Phase 2 study and a lower dose cohort may 
be explored if deemed necessary. Additional patients may be included for further safety and 
tolerability assessments in the LIC as appropriate. The required Schedule of Activities and 
safety review process for the Japanese patient only LIC is outlined in Appendix 9 and 
Appendix 10, respectively. 
A reduced schedule of activities will be followed upon approval of Amendment 8 as 
indicated in Table 1. 

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Add 3 Patients 
for 
Confirmation 
Japan Will 
Join Phase 2 
Japan Will Not 
Join Phase 2 
Figure 2. Japanese Patient-Only Lead-In Cohort Schema 
 
 
 
 
 
DLT ≤1/6 
 
DLT ≥2//6 
 
 
3.3. Drug-Drug Interaction (DDI) and Holter Monitoring Study 
For evaluation of the drug interaction potential of PF-06463922, approximately 30 patients 
(6 evaluable patients with each drug probe) will be administered a single dose of a probe 
substrate alone on Day -2 to determine the exposure of the probe substrate when given 
without PF-06463922. Starting on Cycle 1 Day 1, patients will begin daily dosing of 100 mg 
PF-06463922 QD. On Cycle 1 Day 15, another single dose of the probe substrate will be 
administered concurrently with PF-06463922. 
In consultation with the sponsor and based on the co-medications the patients is expected to 
use concurrently with the probe substrate during the DDI portion (or within 2 weeks prior to 
first dose of probe substrate); at least 6 patients will be assigned to take each of the probe 
substrates listed below. Subjects who withdraw prior to completion of the Cycle 1 
Day 15 DDI assessment or have inadequate assessments for DDI evaluation for any probe 
substrate may be replaced at the sponsor’s discretion (up to a maximum of two). 
DLT >1/3 
DLT = 1/3 
Japanese LIC Patients 
(minimum 3 patients) 
DLT ≤0/3 

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PF-922= PF-06463922 
CHT= continuous holter monitoring 
 
Probe Drugs 
 
Enzyme/ 
Transporter 
Suggested Probe 
CYP2B6 
Bupropion (100-mg single dose) 
CYP2C9 
Tolbutamide (500-mg single dose) 
UGT 
Acetaminophen (500-mg single dose) 
Pgp 
Fexofenadine (60-mg single dose) 
 
Additionally, continuous Holter telemetry of subjects enrolled in this study will be used to 
evaluate the effect of PF-06463922 on the PR interval by comparing the patients pre-drug 
baseline with PR interval observations associated with exposure of PF-06463922 following a 
single dose and at steady state. Twenty-four hour Holter monitoring will be conducted on 
Day -1 through Cycle 1 Day 1, and again on Cycle 1 Day 14. On Day -1, the 24-hour Holter 
monitoring will begin approximately 24 hours after probe substrate administration on Day -2. 
On Cycle 1 Day 14, 24-hour Holter monitoring will begin immediately prior to 
PF-06463922 administration. It is assumed that any inhibition as well as induction of 
metabolic enzymes/transporters due to PF-06463922 will be completed within 15 days of 
continuous dosing of PF-06463922. 
This study will be conducted in approximately 10 participating Phase 2 sites and will begin 
and conclude upon official notification by the sponsor via letter or email. At the time of 
registration, sites will inform Pfizer what concomitant medications a patient is receiving and 
what drug probe is suggested. Patients in the DDI and Holter monitoring study will meet the 
same inclusion and exclusion criteria as required for the main study, with some additional 
criteria specified specifically in Section 4.2. Additionally, patients will only be eligible to 
participate if they meet the prior treatment requirements of EXP groups 2-6. 

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A reduced schedule of activities will be followed upon approval of Amendment 8 as 
indicated in Table 1. 
3.4. Starting Dose 
3.4.1. Phase 1 
The starting dose of PF-06463922 will be 10 mg given once daily (or twice daily), 
continuously in 21-day cycles. 
3.4.2. Phase 2 
Patients will receive PF-06463922 as a single agent at the RP2D determined in Phase 1 once 
daily in 21-day cycles. 
3.4.3. Criteria for Dose Escalation 
In the Phase 1 portion, PF-06463922 will be evaluated at escalating doses of 10, 25, 50, 75, 
100, 150, 200, 250, 300, and 400 mg/once daily (QD) as per Table 9. The doses that will be 
evaluated for BID dosing are provided in Table 13. After the 25 mg dose has been evaluated 
and has cleared the dose-limiting toxicity (DLT) observation period for confirming that 
higher doses may be tested, doses of PF-06463922 will be assigned to each cohort of patients 
using a Continuous Reassessment Method (CRM) model. The goal of the Phase 1 portion is 
to determine the dose of PF-06463922 that is the closest to but no higher than a 33% 
probability of a DLT (ie, a target DLT rate of 0.33). Each dose cohort will initially include at 
least 3 patients evaluable for toxicity within the first cycle. The first 3 patients (ie, the first 
cohort) will be treated at 10 mg QD, and the following dose level explored will be 
25 mg QD. To assign the dose level for each subsequent patient, the probability of DLT is 
estimated to a target rate 33%. This estimate is achieved for each level taking into account 
all the collected toxicity data from all treated patients up to that time and the prior 
expectations of toxicity. Based on the observed toxicity profile, CRM permits dose-level 
skipping during dose escalation. However, in order to prevent overly aggressive dose 
escalation, for every escalation the maximum allowed dose level skipped will be limited to 
one dose level. No restriction is applied for dose de-escalation. 
The probabilities of DLT are estimated based on a Bayesian statistical model with prior 
distribution to learn about the overall dose-toxicity relationship. Patients’ DLT data will be 
reported to the study statistician who will update the dose-toxicity model before the next dose 
level is explored. Details on the CRM method are provided in Section 9.2 and the Statistical 
Analysis Plan. 
Patients who discontinue treatment before completing Cycle 1 (ie, the DLT evaluation time 
window) or receive less than 16 of the planned 21 PF-06463922 doses for reasons other than 
treatment-related toxicity (eg, missed appointments, misplaced study drug supplies, 
development of coexisting medical condition rendering the patient unable to swallow 
medication, development of rapidly progressing disease) will be replaced for DLT evaluation 
but will remain in the overall safety and efficacy analyses. 

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To avoid overly rapid escalation and to retain the efficiency of dose administration when 
enrollment is fast, the following restrictions will be applied: 
• For each dose level, patients will be enrolled in cohorts of minimum 3 patients 
(unless 2 DLTs are observed in the first 2 patients tested at that dose level). The first 
2 patients may enroll together, but the next patient(s) will enroll at least 1 week later. 
The timing of patient enrollment may be further evaluated as safety and PK data 
become available. 
• Enrollment for the next cohort of patients will open when patients on the current dose 
cohort have completed the pre-specified DLT observation period or experienced a 
DLT. 
• Enrollment in dose level cohorts lower than the highest tested dose level cohort may 
occur before the completion of the pre-specified DLT observation period. 
• Dose level skipping in escalation to untested doses will be limited to only one level 
(k →k+2). In particular, at least 3 patients should have been treated for at least one 
cycle at dose level k before escalation to dose level k+2. 
• Dose escalation recommendation by the CRM algorithm may be overruled (but 
frequency should be minimized) by the Sponsor if the nature of the existing data 
causes safety concern. 
• Further exploration of doses lower than those recommended by the CRM model may 
be evaluated based on the totality of the safety data. 
In case the DLT rate at the initial dose level of 10 mg QD exceeds 33%, the dose level of 
5 mg QD will be tested. 
Table 9. 
Phase 1 PF-06463922 Dose Levels 
 
DOSE LEVEL 
(DL)mg mg/day 
Phase 1* 
MDZ DDI# 
Evaluation 
5 
DL -1 
-1 
10 
Starting Dose 
n/a 
25 
DL 2** 
1 
50 
DL 3 
n/a 
75 
DL 4 
2 
100 
DL 5 
150 
DL 6 
3 
200 
DL 7 
250 
DL 8 
4 
300 
DL 9 
400 
DL 10 
* Dose levels may be skipped in the CRM algorithm depending on the observed toxicities. 
**CRM design design commences after the evaluation of toxicities observed in DL2. 
# Potential dose levels (one dose at each level) for MDZ DDI substudy. 
n/a: not applicable 

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Intra-patient dose escalation may be permitted if all of the following conditions are satisfied: 
• Cycle 1 was completed without any DLT; 
• His/her maximum drug-related toxicity during prior cycles of therapy was 
Grade 2 and did not require a dose modification; 
• Observation of Grade 3 laboratory abnormalities not requiring dose modifications 
(as identified in Table 10) would be permitted; 
• Three patients at the next higher dose level have completed Cycle 1 with study drug 
without having a DLT. 
The decision to increase the dose has been approved by discussion with both the Investigator 
and the Sponsor. A patient whose dose has been escalated will not contribute to the 
assessment of the number of DLTs at the escalated dose level. 
Dose administration (dose escalation and de-escalation) within the context of the CRM 
model of the Phase 1 portion of the trial stops if: (1) the maximum sample size has been 
reached (36 in total, see Section 9.3 for details), (2) at least 12 patients have been treated at a 
dose that is predicted to be the MTD or (3) all doses appear to be overly toxic and the MTD 
cannot be determined in the current trial. 
The final posterior probability and 90% posterior probability interval estimates of DLT at 
each dose level will be calculated, with data from all patients that are enrolled and treated. 
Once one of the aforementioned conditions for stopping the CRM is met, the dose identified 
as MTD will be evaluated together with information gathered from PK analyses and the 
overall safety profile. The dose(s) likely to be considered the RP2D will be expanded to 
12 patients if not already tested within the CRM context in order to confirm the RP2D. 
3.5. DLT Definition (Phase 1) 
Severity of adverse events will be graded according to NCI CTCAE version 4.03. For the 
purpose of dose escalation, any of the following adverse events occurring in the first cycle of 
treatment (21 days) which are attributable to PF-06463922. 
Hematologic: 
• Grade 4 neutropenia lasting >7 days. 
• Febrile neutropenia (defined as ANC <1000/mm3 with a single temperature of 
38.3C ((101F) or a sustained temperature of 38C (100.4F) for >1 hour). 
• Grade 3 neutropenic infection. 
• Grade 3 thrombocytopenia with bleeding. 
• Grade 4 thrombocytopenia. 

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Non-Hematologic: 
• Grade 3 pancreatitis. 
• Grade 3 toxicities (excluding Grade 3 laboratory abnormalities not requiring dose 
modifications as indicated in Table 10) persisting after optimal treatment with 
standard medical therapy (eg, anti-emetics, anti-diarrheals). 
• Symptomatic Grade 3 QTc prolongation (QTc 501 msec on at least two separate 
ECGs), or asymptomatic Grade 3 QTc prolongation that has been confirmed by 
repeat testing and re-evaluation by a qualified person, and persists after correction of 
reversible causes such as electrolyte abnormalities or hypoxia. 
• 20% decrease in Left Ventricular Ejection Fraction (LVEF) compared to baseline 
echocardiogram or Multi Gated Acquisition Scan (MUGA) using the same method. 
Other: 
• Failure to deliver at least 16 out of the 21 prescribed daily total doses (approx. 75% 
planned dose for Cycle 1) due to toxicities attributable to study drug. 
• Failure to restart dosing after 21 days (1 cycle) delay due to toxicities attributable to 
study drug. 
3.6. MTD Definition 
The MTD estimate is the highest dose level associated with 33% of patients experiencing a 
DLT. Due to the discreteness of the dose levels and in the interest of safety of patients, the 
estimated MTD is the highest dose level with a DLT rate less than 0.33. 
3.7. Recommended Phase 2 Dose (RP2D) Definition 
The Recommended Phase 2 Dose (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, then this dose usually becomes the RP2D. Further experience 
with the MTD may result in a RP2D lower than the MTD. The final RP2D will be 
communicated by a letter to site investigator participating to the Phase 2. 
3.8. Midazolam DDI Study (Phase 1) 
The potential of PF-06463922 to inhibit/induce CYP3A will be evaluated using MDZ as a 
CYP3A probe substrate. In Phase 1, the MDZ interaction study will be evaluated at 3-4 dose 
levels (fewer dose levels may be evaluated depending on emerging PK results) starting in the 
second PF-06463922 dose level (ie, 25 mg, see Table 9 Section 3.4.3). For this substudy, at 
least 3 evaluable patients per cohort will be assessed for the effect of repeat 
PF-06463922 administration on the pharmacokinetics of midazolam. 

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Patients enrolled in the MDZ interaction substudy will receive a single 2 mg oral dose of 
MDZ on Day –7 and another single 2-mg oral dose of MDZ concurrently with 
PF-06463922 on Cycle 1 Day 15 (morning dose if on BID schedule). 
3.9. Food Effect Study (Phase 1) 
The effect of food on the pharmacokinetics of PF-06463922 will be evaluated in a food effect 
substudy in approximately 6 patients in Phase 1. The testing order for fed versus fasted 
conditions will be as follows: the first half of the patients to participate in this substudy will 
be tested under fed followed by fasted conditions, the next half of the patients will be tested 
under fasted followed by fed conditions. Patients who have had a gastrectomy or have 
dietary or other restrictions that preclude a 10-hour overnight fast (water permitted) or 
consumption of the required high-fat, high-calorie meal will not participate in this sub-study. 
The effect of a high-fat, high-calorie breakfast on PF-06463922 pharmacokinetics will be 
studied. Each patient will serve as his/her own control in which PF-06463922 will be 
administered in the morning under either “fed” or “fasted” conditions on Day (-7) and 
Day 1 of Cycle 1, respectively. After Cycle 1 Day 1 in the food effect cohort only, 
PF-06463922 should be administered with food (ie, normal diet) regardless of which 
condition the patient was last dosed (ie, fed or fasted). 
No trial drug will be administered during the interval between the Day-7 and Day 1 of the 
first cycle. 
3.10. Drug-Drug Interaction and Holter Monitoring Study 
To evaluate the potential interaction of PF-06463922 on drugs that are metabolized via 
pathways that include CYP2B6, CYP2C9, P-gp, and select UGT isoforms, a drug-drug 
interaction study will be conducted in approximately 30 ALK-positive NSCLC patients 
(6 evaluable patients for each drug probe). Additionally, an evaluation of the effects of 
PF-06463922 on the PR interval will be conducted via continuous Holter telemetry 
comparing the subject’s pre-drug baseline values with observations of PR interval changes 
associated with exposure of PF-06463922 following a single dose and again at steady state. 
For patients participating in the DDI and Holter monitoring study, when possible, breakfast, 
lunch and dinner should be consumed at approximately at the same times on days of Holter 
monitoring (Day -1, Cycle 1 Day 1 and Cycle 1 Day 14). On Day -2 and Cycle 1 Day 15, the 
probe substrate should be administered in the fasted state, when possible, (no food at least 
2 hours before through 2 hours after probe substrate dosing). On days of continuous Holter 
monitoring (Day -1, Cycle 1 Day 1 and Cycle 1 Day 14), patients should be advised to not 
undergo any exercise. Additionally on Holter monitoring days substances that may alter 
ECG readings (such as caffeine-containing products, alcohol and tobacco containing 
products) should be avoided. 

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4. PATIENT SELECTION 
Section 4 includes Patient Selection criteria for PF-06463922. When applicable, patients 
who receive crizotinib following PF-06463922 should also follow the Patient Selection 
criteria as outlined in Appendix 11. 
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. 
Baseline assessments (eg, tumor assessments) performed as standard of care and prior to 
signing of the informed consent may be used provided these do not exceed the timelimit 
windows provided in the Schedule of Activities. 
4.1. Inclusion Criteria 
Patient eligibility should be reviewed and documented by an appropriately qualified member 
of the investigator’s study team before patients are included in the study. 
Patients must meet all of the following inclusion criteria to be eligible for enrollment into the 
study: 
1. Evidence of histologically or cytologically confirmed diagnosis of metastatic NSCLC 
(Stage IV, AJCC v7.0) that carries an ALK rearrangement, as determined by the Food 
and Drug Administration (FDA)-approved FISH assay (Abbott Molecular Inc) or by 
Immunohistochemistry (IHC) (Ventana Inc), or a ROS1 rearrangement as determined 
by FISH or RT-PCR or Next Generation Sequencing (NGS) via a local diagnostic test 
(LDT). A central laboratory confirmation by a Sponsor-selected, validated test will 
retrospectively determine final ROS1 status. All patients (ALK positive and 
ROS1 positive) must have archival tissue sample available and collected prior to 
enrollment. 
2. Disease Status Requirements: 
Phase 1: ALK-positive NSCLC patients must either be treatment naïve in the 
advanced setting or have had disease progression after at least 1 previous ALK 
inhibitor therapy(ies). ROS1-positive NSCLC patients must either be treatment naïve 
in the advanced setting or have had disease progression after at least 1 previous 
ROS1 inhibitor therapy(ies). 
Phase 2: 
ALK-positive NSCLC patients must either be or have had: 
• Treatment naïve (ie, no prior chemotherapy in the metastatic disease setting 
and no prior ALK inhibitor therapy allowed). [EXP-1]; 
• Disease progression after crizotinib only. No prior chemotherapy is allowed 
in the metastatic disease setting. [EXP-2]; 

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• Disease progression after crizotinib and 1 or 2 prior regimens of 
chemotherapy in the metastatic disease setting. [EXP-3A]; 
• Disease progression after 1 prior ALK inhibitor therapy other than crizotinib. 
Patients may have had any number of prior chemotherapy regimens in any 
disease setting. [EXP-3B]; 
• Disease progression after 2 prior ALK inhibitor therapies. Patients may have 
had any number of prior chemotherapy regimens in any disease setting. 
[EXP-4]; 
• Disease progression after 3 prior ALK inhibitor therapies. Patients may have 
had any number of prior chemotherapy regimens in any disease setting. 
[EXP-5]. 
ROS1-positive NSCLC patients may be: 
• Treatment naïve (ie, no prior chemotherapy in the metastatic disease setting 
and no prior ROS inhibitor therapy). [EXP-6]; 
• Any number of prior therapies (ie, chemotherapy and/or ROS inhibitor 
therapies). [EXP-6]. 
DDI and Holter Monitoring Study patients may be: 
• ALK-positive or ROS1-positive NSCLC patients who meet the above disease 
status requirements for EXP groups 2-6. 
3. Tumor Requirements: 
Phase 1: All Patients must have at least one measurable target extracranial lesion 
according to RECIST v1.1. In addition patients with asymptomatic CNS metastases 
(including patients asymptomatic by means of stable or decreasing doses of steroids 
within the last 2 weeks prior to study entry) will be eligible. The brain metastases 
may be newly diagnosed or be present as progressive disease after surgery, whole 
brain radiotherapy or stereotactic radiosurgery (see Exclusion Criterion #3 for the 
lapsed time period required between the end of radiotherapy and study entry). 
Patients who have asymptomatic radiologically suspected leptomeningeal disease 
(LM) or carcinomatous meningitis (CM) and negative spinal fluid (CSF) are eligible 
to enter Phase 1. 
Phase 2: All Patients must have at least one measurable target extracranial lesion 
according to RECIST v1.1. In addition patients with asymptomatic CNS metastases 
(including patients controlled with stable or decreasing steroid use within the last 
2 weeks prior to study entry) will be eligible. The brain metastases may be newly 
diagnosed or be present as progressive disease after surgery, whole brain radiotherapy 
or stereotactic radiosurgery (see Exclusion Criterion #3 for the lapsed time period 

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required between the end of radiotherapy and study entry). Patients who have 
leptomeningeal disease (LM) or carcinomatous meningitis (CM) will be eligible if the 
LM/CM is visualized on MRI or if documented baseline cerebral spinal fluid (CSF) 
positive cytology is available. 
DDI and Holter Monitoring Study: All Patients must have at least one measurable 
intracranial or extracranial lesion according to RECIST v1.1 (ie, patients may be 
eligible with only 1 CNS lesion provided it is measurable per RECIST 101). Patients 
with CNS metastases are eligible if they are asymptomatic (including patients 
controlled with stable or decreasing steroid use within the last 2 weeks prior to study 
entry). The brain metastases may be newly diagnosed or be present as progressive 
disease after surgery, whole brain radiotherapy or stereotactic radiosurgery (see 
Exclusion Criterion #3 for the lapsed time period required between the end of 
radiotherapy and study entry). Patients who have leptomeningeal disease (LM) or 
carcinomatous meningitis (CM) will be eligible if the LM/CM is visualized on MRI 
or if documented baseline cerebral spinal fluid (CSF) positive cytology is available. 
4. Age 18 years (or ≥20 years of age if required by local regulation). 
5. ECOG Performance Status (PS): 
• Phase 1: 0 or 1; 
• Phase 2: 0, 1, or 2. 
6. Adequate Bone Marrow Function, including: 
• Absolute Neutrophil Count (ANC) 1.5 x 109/L; 
• Platelets 100 x 109/L; 
• Hemoglobin 9 g/dL. 
7. Adequate Pancreatic Function, including: 
• Serum total amylase 1.5 ULN; 
• Serum lipase 1.5 ULN. 
8. Adequate Renal Function, including: 
• Serum creatinine 1.5 x ULN or estimated creatinine clearance 60 mL/min 
as calculated using the method standard for the institution. 
9. Adequate Liver Function, including: 
• Total serum bilirubin 1.5 x ULN; 

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• Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) 
2.5 x ULN; 5.0 x ULN if there is liver metastases involvement. 
10. Acute effects of any prior therapy resolved to baseline severity or to CTCAE 
Grade 1 except for AEs that in the investigator’ judgment do not constitute a safety 
risk for the patient. 
11. Serum pregnancy test (for females of childbearing potential) negative at screening 
(before the patient may receive the investigational product). A patient is of 
childbearing potential if, in the opinion of the investigator, she is biologically capable 
of having children and is sexually active. 
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. Willingness and ability to comply with the study scheduled visits, treatment plans, 
laboratory tests and other procedures. 
14. Male and female patients of childbearing potential and at risk for pregnancy must 
agree to use two highly effective methods of contraception from the time of the first 
negative pregnancy test at screening, throughout the study and for 97 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. 
Japan Sites Only: A female patient who is not of childbearing potential is one that 
(ie, meets at least one of the following criteria): 
• Has undergone a documented hysterectomy and/or bilateral oophorectomy; 
• Has medically confirmed ovarian failure; or 
• Has achieved postmenopausal status, defined as cessation of regular menses 
for at least 12 consecutive months with no alternative pathological or 
physiological cause (which may be confirmed with a serum 
follicle-stimulating hormone (FSH) level within the laboratory’s reference 
range for postmenopausal women). 
4.2. Exclusion Criteria 
Patients presenting with any of the following will not be included in the study: 
1. Spinal cord compression is excluded unless the patient demonstrates good pain 
control attained through therapy and there is stabilization or recovery of neurological 
function for the 4 weeks prior to study entry. 

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2. Major surgery within 4 weeks of study entry. Minor surgical procedures (eg, port 
insertion) are not excluded, but sufficient time (eg, up to 2 weeks) should have passed 
for wound healing. 
3. Radiation therapy (except palliative to relieve bone pain) within 2 weeks of study 
entry. Palliative radiation (10 fractions) must have been completed at least 48 hours 
prior to study entry. Stereotactic or small field brain irradiation must have completed 
at least 2 weeks prior to study entry. Whole brain radiation must have completed at 
least 4 weeks prior to study entry. 
4. Systemic anti-cancer therapy completed within a minimum of 5 half-lives of study 
entry (unless clinically meaningful tumor flare per discretion of the investigator, in 
which discussion with the sponsor is warranted). 
5. Prior therapy with an antibody or drug specifically targeting T-cell co-stimulation or 
immune checkpoint pathways, including, but not limited to, anti-PD-1, anti-PD-L1, 
anti-PD-L2, anti-CD137, or anti-cytotoxic T lymphocyte associated antigen 
4 (anti-CTLA-4) antibody. 
6. Previous high-dose chemotherapy requiring stem cell rescue. 
7. Prior irradiation to >25% of the bone marrow (see Appendix 5 Bone Marrow Reserve 
in Adults). 
8. Active and clinically significant bacterial, fungal, or viral infection including 
hepatitis B (HBV), hepatitis C (HCV), known human immunodeficiency virus (HIV), 
or acquired immunodeficiency syndrome (AIDS)-related illness. 
9.  Clinically significant cardiovascular disease (that is, active or <3 months prior to 
enrollment): cerebral vascular accident/stroke, myocardial infarction, unstable angina, 
congestive heart failure (New York Heart Association Classification Class ≥ II), 
second-degree or third-degree AV block (unless paced) or any AV block with PR 
>220 msec. 
Ongoing cardiac dysrhythmias of NCI CTCAE Grade ≥2, uncontrolled atrial 
fibrillation of any grade, bradycardia defined as <50 bpm (unless patient is otherwise 
healthy such as long-distance runners, etc.), machine-read ECG with QTc >470 msec, 
or congenital long QT syndrome. 
10. Patients with predisposing characteristics for acute pancreatitis according to 
investigator judgment (eg, uncontrolled hyperglycemia, current gallstone disease, 
alcoholism [more than 4 drinks on any day or 14 drinks per week where 1 drink is 
defined as the alcoholic beverage containing approximately 14 grams of pure alcohol, 
eg, 12 fl oz/360 mL regular beer or 5 fl oz/150 mL of wine] in the last month. 

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11. History of extensive, disseminated, bilateral or presence of Grade 3 or 4 interstitial 
fibrosis or interstitial lung disease including a history of pneumonitis, hypersentivity 
pneumonitis, interstitial pneumonia, interstitial lung disease, obliterative bronchiolitis 
and pulmonary fibrosis. Patients with history of prior radiation pneumonitis are not 
excluded. 
12. 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. 
13. 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. 
14. Evidence of active malignancy (other than current NSCLC, non-melanoma skin 
cancer, in situ cervical cancer, papillary thyroid cancer, DCIS of the breast or 
localized and presumed cured prostate cancer) within the last 3 years. 
15. Active inflammatory gastrointestinal disease, chronic diarrhea, symptomatic 
diverticular disease or previous gastric resection or lap band. 
16. Current use or anticipated need for food or drugs that are known strong or moderate 
CYP3A4 inhibitors, including their administration within 10 days prior to the first 
PF-06463922 dose (ie, strong CYP3A4 inhibitors: 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; Moderate CYP3A4 inhibitors: 
erythromycin, verapamil, atazanavir, delavirdine, fluconazole, darunavir, diltiazem, 
aprepitant, imatinib, tofisopam, ciprofloxacin, cimetidine). Concomitant medication 
with a suspected CYP3A4 inhibitory effect must be approved by the Sponsor. 
17. Current use or anticipated need for drugs that are known strong CYP3A4 inducers, 
including their administration within 12 days prior to the first PF-06463922 dose 
(ie, phenobarbital, rifampin, phenytoin, carbamazepine, rifabutin, rifapentin, 
clevidipine, St. John’s Wort). Concomitant medication with a suspected 
CYP3A4 inductive effect must be approved by the Sponsor. 
18. Concurrent use of drugs that are CYP3A4 substrates with narrow therapeutic indices, 
such as astemizole, terfenadine, cisapride, pimozide, quinidine, tacrolimus, 
cyclosporine, sirolimus, (alfentanil and fentanyl, including transdermal patch) or 
ergot alkaloids (ergotamine, dihydroergotamine) is not permitted or caution is 
warranted. Concomitant medication suspected of being a CYP3A4 substrate with 
narrow therapeutic index must be approved by the Sponsor. 

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19. Concurrent use of drugs that are CYP2C9 substrates with narrow therapeutic indices, 
such as warfarin, phenytoin or a sensitive substrate such as celecoxib is not permitted 
or caution is warranted. Concomitant medication suspected of being a 
CYP2C9 substrate with narrow therapeutic index must be approved by the Sponsor. 
20. Concurrent use of drugs that are sensitive CYP2B6 substrates, such as bupropion, 
efavirenz is not permitted or caution is warranted. Concomitant medication suspected 
of being a CYP2B6 substrate with narrow therapeutic index must be approved by the 
Sponsor. 
21. Current use or anticipated need for drugs that are known strong CYP2C19 inhibitors, 
including their administration within 12 days prior to study entry (ie, fluconazole, 
fluvoxamine, ticlopidine). Concomitant medication with a suspected 
CYP2C19 inhibitory effect must be approved by the Sponsor. 
22. Current use or anticipated need for drugs that are known strong CYP2C8 inhibitors, 
including their administration within 12 days prior to study entry (ie, 
gemfibrozil). Concomitant medication with a suspected CYP2C8 inhibitory effect 
must be approved by the Sponsor. 
23. Current use or anticipated need for drugs that are known P-gp substrates with a 
narrow therapeutic index, including their administration within 12 days prior to study 
entry (ie, digoxin). Concomitant medication with a suspected P-gp substrates with a 
narrow therapeutic index must be approved by the Sponsor. 
24. Patients presenting with abnormal Left Ventricular Ejection Fraction (LVEF) by 
echocardiogram or Multi-Gated Acquisition Scan (MUGA) according to institutional 
lower limits. 
25. Breastfeeding female patients (including patients who intend to interrupt 
breastfeeding). 
Additional Exclusion Criteria for Patients participating in the Drug-drug Interaction 
Holter Monitoring Study: 
1. CYP2B6: for the DDI evaluation with buproprion, aCYP2B6 probe substrate, patients 
should not be taking any moderate/strong inhibitors or inducers of CYP2B6 within 
2 weeks of the lead-in probe substrate dosing and until the DDI assessment portion is 
completed on Day 15 of Cycle 1. Refer to the buproprion product insert for complete 
information on contraindications. 
2. CYP2C9: for the DDI evaluation with tolbutamide, a CYP2C9 probe substrate, 
patients should not be taking any moderate/strong inhibitors or inducers of 
CYP2C9 within 2 weeks of the lead-in probe substrate dosing and until the DDI 
assessment portion is completed on Day 15 of Cycle 1. Please refer to the 
tolbutamide product insert for complete information on use and contraindications. 

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3. UGTs: for the DDI evaluation with acetaminophen, a UGT probe substrate, patients 
subjects should not be taking any moderate/strong inhibitors or inducers of UGTs 
within 2 weeks of the lead-in probe substrate dosing and until DDI assessment 
portion is completed on Day 15 of Cycle 1. Refer to acetaminophen product insert 
for complete information. 
4. P-gp: for the DDI evaluation with fexofenadine, a probe substrate for P-gp, patients 
should not be taking any moderate/strong inhibitors or inducers of P-gp within 
2 weeks of the lead-in probe substrate dosing and until DDI assessment portion is 
completed on Day 15 of Cycle 1. Refer to fexofenadine product insert for complete 
information. 
5. All subjects with a history of risk factors for QT prolongation or torsades de pointes 
(eg, organic heart disease, congestive heart failure, hypokalemia, hypomagnesemia, 
congenital long QT syndrome, myocardial ischemia or infarction) will be excluded 
from this cohort. 
4.3. Life Style Guidelines 
4.3.1. Contraception 
PF-06463922 is teratogenic and an aneugen, and can therefore cause harm when 
administered to a pregnant woman. Therefore, use of a highly effective method of 
contraception during treatment with this study drug is mandatory. 
The investigator or his or her designee, in consultation with the participant, will confirm that 
the participant has selected a highly effective method of contraception for the individual 
participant and his or her partner(s) from the permitted list of contraception methods (see 
below, Section 4.3.1.2) and will confirm that the participant has been instructed in its 
consistent and correct use. At time points indicated in the schedule of assessments, the 
investigator or designee will inform the participant of the need to use a highly effective 
method of contraception consistently and correctly and document the conversation and the 
participant’s affirmation in the participant’s chart (participants need to affirm their consistent 
and correct use of at least one of the appropriate methods of contraception). 
The investigator, at each study visit, will discuss with the patient the need to use a highly 
effective contraception consistently and correctly and document such conversation in the 
patient chart. In addition, the investigator will instruct the patient to call immediately if a 
selected birth control method is discontinued or if pregnancy is known or suspected. 
Women of childbearing potential enrolled in the study (WOCBP, definition provided below, 
Section 4.3.1.1) must agree to use a nonhormonal method of contraception. PF-06463922 
can render hormonal contraceptives ineffective because they are metablized by CYP3A, 
which may be induced by PF-06463922. If a hormonal method of contraception is 
unavoidable, then a condom must be used in combination with the hormonal method. 
Contraception must be continued for at least 21 days after completing therapy. 

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During treatment with PF-06463922, all sexually active male patients must agree to prevent 
potential transfer to and exposure of partner(s) to PF-06463922 through ejaculate by using a 
condom consistently and correctly, beginning with the first dose of investigational product 
and continuing for at least 97 days after the last dose of PF-06463922. Male patients with 
pregnant partners must be agreed to use condoms. Male patients must agree to refrain from 
donating sperm throughout the study and for 97 days after the last dose of assigned treatment. 
4.3.1.1. Woman of Childbearing Potential (WOCBP) 
A woman is considered fertile following menarche and until becoming postmenopausal 
unless permanently sterile (see below). 
If fertility is unclear (eg, amenorrhea in adolescents or athletes) and a menstrual cycle cannot 
be confirmed before the first dose of study intervention, additional evaluation should be 
considered. 
Women in the following categories are not considered WOCBP: 
1. Premenopausal female with 1 of the following: 
Documented hysterectomy; 
Documented bilateral salpingectomy; 
Documented bilateral oophorectomy. 
For individuals with permanent infertility due to an alternate medical cause other than 
the above, (eg, mullerian agenesis, androgen insensitivity), investigator discretion 
should be applied to determining study entry. 
Note: Documentation for any of the above categories can come from the site 
personnel’s review of the participant’s medical records, medical examination, or 
medical history interview. The method of documentation should be recorded in the 
participant’s medical record for the study. 
2. Postmenopausal female: 
A postmenopausal state is defined as age 60 years or older or no menses for 
12 months without an alternative medical cause. 
• A high follicle-stimulating hormone (FSH) level in the postmenopausal range 
may be used to confirm a postmenopausal state in women not using hormonal 
contraception or hormone replacement therapy (HRT). 
• Females on HRT and whose menopausal status is in doubt will be required to use 
one of the nonestrogen hormonal highly effective contraception methods if they 
wish to continue their HRT during the study. Otherwise, they must discontinue 
HRT to allow confirmation of postmenopausal status before study enrollment. 

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4.3.1.2. Contraception Methods 
1. Established use of oral, inserted, injected or implanted hormonal methods of 
contraception are allowed provided a condom is used in combination with the 
hormonal method. The patient must have 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 must be used in association with a highly effective female method of 
contraception. 
4. Male sterilization with appropriately confirmed absence of sperm in the 
post-vasectomy ejaculate. 
5. Bilateral tubal ligation or bilateral salpingectomy. 
4.3.2. Sunlight Exposure 
Patients will be advised to report any reaction to sun exposed skin. In addition, special 
precautions will be taken to limit any potential photo irritation effect, by minimizing the 
patients’ exposure to light including high intensity UVb sources such as tanning beds, 
tanning booths and sunlamps. Patients should be advised to apply sunscreen and wear 
appropriate clothing to minimize exposure to the sun during treatment with PF-06463922. 
4.3.3. Additional Lifestyle Guidances 
Patients will be advised to avoid eating or drinking grapefruit/grapefruit related citrus fruits 
[eg, Seville oranges, pomelos] that strongly inhibit/induce CYP3A (refer to Section 5.3). 
Because there are no available data on concurrent alcohol use with PF-06463922, patients 
should be advised to limit alcohol consumption during the study treatment period. 
4.4. Sponsor Qualified Medical Personnel 
The contact information for the Sponsor's appropriately qualified medical personnel for the 
trial is documented in the study contact list located in the team Sharepoint site/study portal. 
To facilitate access to appropriately qualified medical personnel on study related medical 
questions or problems, patients are provided with a contact card. The contact card contains, 
at a minimum, protocol and investigational compound identifiers, patient study number, 
contact information for the investigational site and contact details for a help desk in the event 
that the investigational site staff cannot be reached to provide advice on a medical question 
or problem originating from another healthcare professional not involved in the patients 
participation in the study. The help desk number can also be used by investigational staff if 
they are seeking advice on medical questions or problems, however it should only be used in 
the event that the established communication pathways between the investigational site and 
the study team are not available. It is therefore intended to augment, but not replace the 
established communication pathways between the investigational site and study team for 
advice on medical questions or problems that may arise during the study. The help desk 

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number is not intended for use by the patient directly and if a patient calls that number they 
will be directed back to the investigational site. 
4.5. Mini Mental State Examination (MMSE) Rater Qualifications (Phase 1 only; No 
longer required per Amendment 6) 
The Mini Mental State Examination (MMSE) rater administration instructions will be 
provided in the Study Manual and these along with the tool can be found in the publication of 
Folstein et al, 1975.37 The rater must hold a degree, certificate, or license to practice in a 
health care profession or occupation, including (but not limited to) the following: clinical 
psychology, medicine, neurology, neuropsychology, nursing, occupational therapy and other 
allied health care professions, physicians' assistants, psychiatry, school psychology, social 
work, speech-language pathology; plus appropriate training and experience in the ethical 
administration, scoring, and interpretation of clinical behavioral assessment instruments. 
The rater may be any one of the site staff who have contact with the patient on a regular basis 
eg, study co-ordinator, sub investigator, research nurse, principal investigator. 
4.6. Rater Requirements for Assessment of Mood and Assessment of Suicidal Ideation 
and Behavior (Phase 2 only) 
A rater is defined an individual(s) who administers the Columbia Suicide Severity Rating 
Scale43 (C-SSRS) and/or the Beck Depression Inventory-II (BDI-II) scale to patients in the 
study. At least 2 raters will be identified at each site and trained to administer the C-SSRS 
and the BDI-II to patients enrolled in Phase 2. 
5. STUDY TREATMENTS 
Section 5 includes Study Treatment details for PF-06463922. When applicable, patients who 
receive crizotinib following PF-06463922 should follow Study Treatment details as outlined 
in Appendix 11. 
5.1. Allocation to Treatment 
In Phase 1 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 fax or email a complete Registration Form to the designated Sponsor study 
team member. Registration will be within 2 days prior to lead -in single dose as appropriate. 
The Sponsor will assign a patient identification number, which will be used on all Case 
Report Form (CRF) pages and other trial-related documentation or correspondence 
referencing that patient and fax or 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 

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• 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. 
Patient registration to Phase 2 will utilize an automated registration system where a 
randomization number will be assigned. Study treatment should begin approximately 2 days 
after the patient is registered. 
For patients participating in the DDI and Holter monitoring study, registration should occur 
within 2 days of administration of the probe drug . Sites will inform Pfizer of the 
concomitant medications that a patient is receiving and suggested probe drug. 
5.2. Drug Supplies 
5.2.1. Formulation and Packaging 
PF-06463922: In Phase 1, PF-06463922 will be supplied for oral administration as, 25 mg 
and 100 mg acetate solvate tablets in HDPE (High Density Polyethylene) bottles with 
desiccant. Tablets have different sizes and shapes according to different strengths. Study 
medication will be supplied by Pfizer. In Phase 2, PF-06463922 will be supplied for oral 
administration as 25 mg free base tablets in HDPE (High Density Polyethylene) bottles with 
desiccant. Study medication will be supplied by Pfizer. 
Midazolam (MDZ) [Phase 1 only]: Midazolam (2 mg/mL, oral syrup) will be used in the 
study and supplied by the Sponsor. 
Drug –drug Interaction and Holter Monitoring study Probe Drugs (DDI/Holter study 
only): The suggested probe drugs bupropion, tolbutamide, acetaminophen or fexofenadine 
will be used and supplied by the participating study sites. 
5.2.2. Preparation and Dispensing 
Only qualified personnel who are familiar with procedures that minimize undue exposure to 
them and to the environment should undertake the preparation, handling, and safe disposal of 
chemotherapeutic agents. 
5.2.2.1. PF-06463922 
In Phase 1, PF-06463922 will be provided in bottles containing 25 mg, or 100 mg acetate 
solvate tablets. The bottles will be labeled with different color labels to differentiate between 
dosage strengths. 
In Phase 2, PF-06463922 will be provided in bottles containing 25 mg free base tablets. 
Site personnel must ensure that patients clearly understand the directions for self-medication. 
Patients should be given sufficient supply to last until their next study visit. Patients will be 
provided with Drug Adminstration Cards and Patient Diaries. In addition, administration 
instructions will be detailed in the Investigational Product (IP) Manual. 

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PF-06463922 will be dispensed at the beginning of each treatment cycle (or as otherwise 
indicated). Patients should be instructed to keep their medication in the bottles provided and 
not transfer it to any other container. 
5.2.2.2. Midazolam (Phase 1 Only) 
Midazolam will be dispensed using the manufacturer specified dispensing instructions. 
Qualified personnel will prepare and dispense the MDZ dose in accordance with the current 
package insert. 
5.2.2.3. Drug-drug Interaction and Holter Monitoring Study Probe Drugs 
The probe drugs will be dispensed using the manufacturer specified dispensing instructions. 
Qualified personnel will prepare and dispense the probe drug dose in accordance with the 
current package insert. The recommended individual probe drugs and their doses for 
administration are outlined in Section 3.3. 
5.2.2.4. PF-06463922 
All patients will receive single-agent PF-06463922. 
The starting dose for PF-06463922 in the Phase 1 will be 10 mg. PF-06463922 will be 
administered once daily (or twice daily) in 21-day cycles. Patients in the Phase 2 will receive 
PF-06463922 as a single agent at the RP2D of 100 mg once daily in 21-day cycles. 
Administration will be performed on an outpatient basis. PF-06463922 should be taken with 
at least 8 oz (240 mL) of water and may be taken with or without food. See 
Section 5.2.3.1 for dosing instructions in food effect cohort (Phase 1 only). Patients should 
be instructed to take their medication at approximately the same time each day and to not 
take more than the prescribed dose at any time. However, a variance of up to 12 hours is 
allowed for any given dose, rather than miss a day’s dose. For patients receiving BID dosing 
(Phase 1 only), study medication should be taken approximately 12 hours apart; however, a 
3-hour variance is allowed. 
If a patient misses a daily dose, they must be instructed not to “make it up” the next day. If a 
patient vomits anytime after taking a dose, they must be instructed not to “make it up,” but to 
resume subsequent doses the next day as prescribed. If a patient inadvertently takes 1 extra 
dose during a day, the patient should not take the next dose of PF-06463922. Patients should 
also be instructed to swallow the trial medication whole and not chew the tablet prior to 
swallowing. No tablet should be ingested if it is broken, cracked, or otherwise not intact. 
Doses may be modified according to Table 10. Patients requiring dose reduction in 
Phase 1 should undergo reduction to the next lower dose level as outlined in 
Table 11 (Table 13 for BID dose levels). Patients requiring dose reduction in Phase 2 should 
undergo reduction to the next lower dose level as outlined in Table 12. Patients must be 
instructed to record all doses (and missed or vomited doses) in a dosing diary supplied by the 
site. If doses are missed or vomited, this must be indicated in the source documents and 
CRFs. 

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For patients participating in the MDZ DDI study (Phase 1), PF-06463922 will be 
administered with MDZ on Cycle 1 Day 15 (morning dose if on BID dosing schedule). 
For patients participating in the food effect study (Phase 1), PF-06463922 will be 
administered following an overnight fast of at least 10 hours on Cycle 1 Day -7 and 
Cycle 1 Day 1. 
For patients participating in the DDI and Holter monitoring study, when possible, breakfast, 
lunch and dinner should be consumed at approximately at the same times on days of Holter 
monitoring (Day -1, Cycle 1 Day 1 and Cycle 1 Day 14). On Day -2 and Cycle 1 Day 15, the 
probe substrate should be administered in the fasted state, when possible (no food at least 
2 hours before through 2 hours after probe substrate dosing). On days of continuous Holter 
monitoring (Day -1, Cycle 1 Day 1 and Cycle 1 Day 14), patients should be advised to not 
undergo any exercise. Additionally on Holter monitoring days substances that may alter 
ECG readings (such as caffeine-containing products, alcohol and tobacco containing 
products) should be avoided. 
In all study parts, patients will continue with the study treatment until progression of disease 
as determined by the investigator, unacceptable toxicity, death or consent withdrawal. 
Patients may continue PF-06463922 treatment after objective progression of disease is 
determined if the patient is continuing to experience clinical benefit, in the opinion of the 
investigator, and after discussion with the Sponsor. 
The study investigator may implement PF-06463922 dose suspension and/or reduction in 
order to ensure patient safety at any time in the course of the study (see Recommended Dose 
Modifications). 
5.2.2.5. Midazolam (Phase 1) 
In the MDZ interaction sub-study, patients will receive a single 2 mg oral dose of MDZ on 
Day -7 and will receive another single 2 mg oral dose of MDZ concurrently with 
PF-06463922 on Cycle 1 Day 15 (morning dose if on BID dosing schedule). 
Patients should refrain from food and beverages (except water) 8 hours prior to MDZ dosing 
and 2 hours after dosing. Qualified personnel will administer MDZ syrup (1 mL to provide 
2 mg of MDZ) using an oral disposable syringe followed by 8 oz (240 ml) of ambient 
temperature water. Additionally, to standardize conditions for PK sampling, patients should 
refrain from lying down (except as needed for vital sign and ECG assessments) in the 2-hour 
period following MDZ administration. 
5.2.3. Food Requirements (Phase 1) 
5.2.3.1. Patients Not Included in the Food Effect Cohort 
Oral PF-06463922 will be administered QD/BID with at least 8-oz (240 mL) of water on an 
empty stomach (morning dose if the patient is on the BID dosing schedule). No food or 
liquids other than water will be consumed for 2 hours before and 2 hours following each dose 
throughout the study. These fasting requirements may be removed (via a letter to the 
investigators) if the data from the food effect substudy indicate that there is no effect of food 
on the bioavailability of PF-06463922. 

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5.2.3.2. Requirements for the Food Effect Cohort 
A food effect substudy will be conducted in Phase 1 at selected dose levels to evaluate the 
effect of a high-fat, high-calorie breakfast on PF-06463922 pharmacokinetics will be studied 
(morning dose if the patient is on the BID dosing schedule). For all patients participating in 
the food effect substudy, PF-06463922 will be administered following an overnight fast of at 
least 10 hours. For those patients scheduled to receive the “fed” treatment, a test breakfast 
meal (described below) will be provided and must be consumed over 30 minutes. Study drug 
will be administered with approximately 8-oz (240 ml) of water 30 minutes after the start of 
the meal. No additional food will be allowed until at least 4 hours post-dose. For patients 
scheduled to receive the “fasted” treatment, study drug will be administered with 8 ounces 
(240 mL) of water. No food will be allowed for an additional 4 hours post-dose. For either 
treatment day, water will be allowed ad libitum except for 1 hr before and 1 hr after drug 
administration. 
After Cycle 1 Day 1 in the food effect cohort only, PF-06463922 should be administered 
with food (ie, normal diet) regardless of which condition the patient was last dosed (ie, fed or 
fasted). 
The test meal to be consumed will be a high-fat (approximately 50% of total caloric content 
of the meal) and high-calorie (approximately 800-1000 calories) meal. This test meal should 
derive approximately 150, 250, and 500-600 calories from protein, carbohydrate, and fat, 
respectively. An example test meal would be 2 eggs fried in butter, 2 strips of bacon (may be 
replaced with ham and cheese of similar caloric content), 2 slices of toast with butter, 
4 ounces of hash brown potatoes, and 8 ounces of whole-fat milk. Substitutions to this test 
meal can be made after discussion with the Sponsor, as long as the meal provides a similar 
amount of calories from protein, carbohydrate, and fat and has comparable meal volume and 
viscosity (if substitutions are made, the contents of the meal will be documented by a 
dietitian or designate to confirm it matches the FDA requirements for protein, carbohydrate 
and fat described above). However, it is understood that some patients may not be able to 
consume the entire meal. Study staff should record the percent of the test meal breakfast and 
the time it takes to be consumed. 
5.2.4. Recommended Dose Modifications 
Every effort should be made to administer study treatment on the planned dose and schedule. 
In the event of significant toxicity dosing may be withheld and/or reduced as described in the 
tables 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 of an oral medication given continuously may occur in two ways: 
• Within a cycle: dosing interruption until adequate recovery and dose reduction, if 
required, during a given treatment cycle; this may persist delaying the start of a new 
cycle. 

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• In the next cycle: dose reduction may be required in a subsequent cycle based on 
toxicity experienced in the previous cycle. 
5.2.5. Dosing Interruptions 
Appropriate follow up assessments should be done until adequate recovery occurs as 
assessed by the Investigator. Criteria required before treatment can resume are described in 
the dose modification tables. 
Doses may be held as needed until toxicity resolution. Depending on when the adverse event 
resolved, a treatment interruption may lead to the patient missing all subsequent planned 
doses within that same cycle or even to delay the initiation of the subsequent cycle. 
If the adverse event that led to the treatment interruption recovers within the same cycle, then 
re-dosing in that cycle is allowed. Doses omitted for toxicity are not replaced within the 
same cycle. The need for a dose reduction at the time of treatment resumption should be 
based on the criteria defined in the Dose Modification Tables unless expressly agreed 
otherwise following discussion between the Investigator and the Sponsor. If a dose reduction 
is applied in the same cycle, the patient will need to return to the clinic to receive new drug 
supply. 
In the event of a treatment interruption for reasons other than treatment-related toxicity 
(eg, elective surgery) lasting >1 week, treatment resumption will be decided in consultation 
with the Sponsor. 
Patients not recovering from PF-06463922 related toxicity within 42 day since last dose 
should discontinue PF-06463922 treatment. 
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. Every effort should be 
made to maintain the tumor assessments scheduling as described in Schedule of Activities 
ie, every 6 weeks (1 week) versus the date of Cycle 1 Day 1. 
5.2.6. Dose Reductions 
Following dosing interruption or cycle delay due to toxicity, the PF-06463922 dose may need 
to be reduced when treatment is resumed. 
In cases where no specific dose adjustments for Grade 1 or Grade 2 treatment-related toxicity 
investigators should always manage their patients according to their medical judgment which 
may include dose reduction or interruption 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. 

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Dose reduction of PF-06463922 (Table 11 for QD dose levels in Phase 1, Table 12 for QD 
dose levels in Phase 2 and Table 13 for BID dose levels in Phase 1) will be allowed 
depending on the type and severity of toxicity encountered (Table 10). Patients requiring 
more than 3 dose reductions will be discontinued from the treatment and entered into the 
follow-up phase, unless otherwise agreed between the Investigator and the Sponsor. All dose 
modifications/adjustments must be clearly documented in the patient's source notes and 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 allowed per investigator discretion for appropriate patient management. 
Patients experiencing a DLT (Phase 1 only) may resume dosing at the next lower dose level 
(if applicable) once adequate recovery is achieved. 
5.2.7. Dose Modifications 
PF-06463922 
Patients will be monitored closely for toxicity, and the dose of PF-06463922 may be 
adjusted. Patients requiring dose reduction per Table 10 should undergo reduction to the 
next lower dose level as outlined in Table 11 for Phase 1 and Table 12 for Phase 
2 (Table 13 for BID dosing). 
Table 10. PF-06463922 Dose Modifications for PF-06463922-Related Toxicities 
Non-Hematologic Toxicities 
 
Toxicity 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Pancreatitis 
If both amylase and lipase are Grade ≤2 in the 
absence of radiological findings of pancreatitis: 
continue at the same dose level without dosing 
interruption. Repeat lipase and amylase. 
If radiologically confirmed pancreatitis: withhold 
dose. Repeat radiology and lipase and amylase 
weekly. If appropriate, resume treatment at one dose 
level lower if radiology has returned to baseline and 
lipase and amylase are Grade ≤2. 
Discontinue 
Discontinue 
Pneumonitis 
(in the absence 
of disease 
progression, 
pulmonary 
embolism, 
positive 
cultures or 
radiation 
effect) 
Withhold lorlatinib until symptoms have returned to 
baseline and consider initiating corticosteroids. 
Resume lorlatinib at 1 reduced dose level. 
Permanently discontinue lorlatinib if 
ILD/pneumonitis recurs or fails to recover after 
6 weeks of lorlatinib hold and steroid treatment 
Discontinue 
Discontinue 
Prolonged QTc 
interval 
Assess electrolytes and 
concomitant 
Assess electrolytes and 
concomitant medications. 
Withhold dose. 
Assess 
Discontinue 

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Toxicity 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
medications. 
Correct any electrolyte 
abnormalities, or 
hypoxia. 
Continue at the same 
dose level. 
Correct any electrolyte 
abnormalities, or hypoxia. 
Continue at the same dose 
level. 
electrolytes and 
concomitant 
medications. 
Correct any 
electrolyte 
abnormalities, or 
hypoxia. 
Upon recovery to 
Grade 1 resume 
treatment at one 
dose level lower. 
LVEF 
Dysfunction 
Not Applicable 
Not Applicable 
Discontinue 
Discontinue 
Other 
(see separate 
tables below 
for Lipid and 
CNS toxicities 
and subsection 
on PR Interval 
Prolongation 
below). 
Consider no dose modification or reduce by one dose 
level, as clinically indicated. 
Withhold dose 
until toxicity is 
Grade 1(or has 
returned to 
baseline), then 
reduce the dose 
by 1 level or 
rechallenge at the 
same dose. 
Withhold dose 
until toxicity is 
Grade 1(or has 
returned to 
baseline), then 
reduce the dose by 
1 level. Or 
discontinue at the 
discretion of the 
investigator. 
Hematologic Toxicities 
 
Toxicity 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Lymphopenia 
Continue at the 
same dose level. 
Continue at the 
same dose level. 
If no evidence of 
infection or other 
clinically 
significant toxicity, 
continue at the 
same dose; 
otherwise, withhold 
dose until toxicity 
is Grade 1 (or 
baseline) then 
rechallenge at the 
same dose or 
reduce the dose by 
1 dose level. 
If no evidence of 
infection or other 
clinically 
significant 
toxicity, continue 
at same dose; 
otherwise, 
withhold dose 
until toxicity is 
Grade 1 (or 
baseline), then 
rechallenge at the 
same dose or 
reduce the dose by 
1 dose level. 
Other 
Consider no dose modification or reduce 
by one dose level, as clinically indicated. 
Withhold dose until toxicity is 
Grade 2 (or has returned to baseline), 
then reduce the dose by 1 dose level. 

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Lipid Elevation Toxicities 
 
Toxicity 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Total Cholesterol 
Continue at the same dose. Introduce or 
modify lipid-lowering therapy. 
Introduce the use of 
a statin or other 
lipid lowering agent 
as appropriate, or 
increase the dose of 
ongoing statin/lipid 
lowering agent, or 
change to a new 
agent. Either 
continue study drug 
at the same dose 
without interruption 
or withhold dose 
until toxicity is 
Grade ≤2 and then 
continue at the 
same dose. 
Introduce the use 
of a statin or other 
lipid lowering 
agent as 
appropriate, or, 
increase the dose 
of ongoing statin/ 
lipid lowering 
agent, or change 
to a new agent. 
Withhold dose 
until toxicity is 
Grade ≤2 and then 
reduce the dose by 
1 dose level or 
rechallenge at the 
same dose. 
Triglycerides 
Continue at the same dose. Introduce or 
modify lipid-lowering therapy. 
Introduce the use of 
a statin or other 
lipid lowering agent 
as appropriate, or 
increase the dose of 
ongoing statin/lipid 
lowering agent or 
change to a new 
agent. Either 
continue study drug 
at the same dose 
without interruption 
or withhold dose 
until toxicity is 
Grade ≤2 and then 
continue at the 
same dose. 
Introduce the use 
of a statin or other 
lipid lowering 
agent as 
appropriate, or 
increase the dose 
of ongoing 
statin/lipid 
lowering agent or 
change to a new 
agent. Withhold 
dose until toxicity 
is Grade ≤2 and 
then reduce the 
dose by 1 dose 
level or 
rechallenge at the 
same dose. 
 
CNS Effect Toxicities 
 
Toxicity 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
CNS effects* 
Continue at the 
same dose or 
withhold dose until 
recovery to baseline 
and then continue at 
the same dose. 
Withhold dose until toxicity is Grade ≤1. 
Reduce dose to the next lower dose. 
Discontinue 
* Examples of CNS effects could include changes in speech, memory, sleep, cognition, or vision. 

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PR Interval Prolongation 
PR-interval prolongation has been observed in patients receiving PF-06463922. Below are 
guidelines for patients who develop first-degree, second-degree, or complete heart block. 
Guidelines distinguish between asymptomatic vs. symptomatic heart block. Symptoms that 
could be attributed to heart block include, but are not limited to include, dizziness, 
lightheadedness, and fatigue, shortness of breath, fainting and palpitations. 
If a patient develops second-degree or third-degree heart block, discussion with the sponsor 
is warranted to discuss appropriate management. 
 
Event 
Asymptomatic 
Symptomatic 
First-degree heart block 
(PR-interval ˃200 msec) 
No dose hold or reduction needed. Assess 
concomitant medications and assess and 
correct electrolyte imbalance that may 
prolong PR interval. Monitor closely by 
obtaining pre-dose ECG at next visit, even 
if unscheduled. Instruct patient to call if 
symptoms develop that may be related to 
heart block. 
Withhold dose. Assess 
concomitant medications, and 
assess and correct electrolyte 
imbalance that may prolong PR 
interval. Obtain ECG in 
approximately 48 hours and 
re-assess symptoms and 
PR-interval. Restart at reduced 
dose when symptoms resolve. 
Second-degree heart 
block 
Withhold dose. Assess concomitant 
medications, and assess and correct 
electrolyte imbalance that may prolong PR 
interval. Repeat ECG in approximately 
48 hours. Instruct patient to call if 
symptoms develop that may be related to 
heart block. Restart at reduced dose if 
subsequent ECG does not show 2nd degree 
block. 
Withhold dose. Refer for cardiac 
observation and monitoring. 
Consider pacemaker placement if 
symptomatic heart block persists. 
Resume at reduced dose only when 
symptoms resolve AND 2nd 
degree block resolves. If patients 
revert to 1st degree block with no 
symptoms, resume at reduced dose. 
Complete Heart Block 
Withhold dose. Refer for cardiac observation and monitoring. Temporary 
pacemaker placement may be indicated for severe symptoms associated with heart 
block. If heart block does not resolve, placement of a permanent pacemaker may 
be considered. 
If pacemaker placed, may resume at full dose. 
If no pacemaker placed, restart at reduced dose only when symptoms resolve AND 
PR <200 msec. 
 
Additionally, for patients with PR interval prolongation, the concomitant use of medicinal 
products known to prolong PR interval is not advised and these should be used with caution 
(see Appendix 12). 

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Table 11. Phase 1 PF 06463922 QD Dose Level Reductions 
 
Current Dose Level 
Dose Level -1 
Dose Level -2 
200 mg QD 
150 mg QD 
100 mg QD 
150 mg QD 
100 mg QD 
50 mg QD 
100 mg QD 
50 mg QD 
25 mg QD 
75 mg QD 
50 mg QD 
25 mg QD 
50 mg QD 
25 mg QD 
N/A 
 
Table 12. Phase 2 PF 06463922 QD Dose Level Reductions 
 
Current Dose Level 
Dose Level -1 
Dose Level -2 
Dose Level -3 
100 mg QD 
75 mg QD 
50 mg QD 
25 mg QD 
 
BID dosing schedules in Phase 1 may include 75 mg BID, 50 mg BID, 35 mg BID, and 
25 mg BID. Additional dose levels may be considered for BID dosing depending on 
emerging safety and PK data. Dose reductions for patients receiving BID dosing should be 
based on Table 10 above and Table 13 below. Additional doses to select for BID dosing and 
additional reduction modification guidelines may be communicated to sites in the form of 
letters to investigators. 
Table 13. PF-06463922 BID Dose Levels (Phase 1) 
 
Current Dose Level 
Dose Level -1 
Dose Level -2 
75 mg BID 
50 mg BID 
25 mg BID* 
50 mg BID 
35 mg BID 
25 mg BID* 
35 mg BID 
25 mg BID 
10 mg BID* 
25 mg BID 
10 mg BID 
5 mg BID 
*Further dose reduction to the next lower dose schedule in this table in patients who are otherwise benefiting 
from PF-06463922 treatment may be permitted after discussion with the Sponsor’s medical monitor. 
 
 
5.2.8. Compliance 
Patients will be required to return all unused PF-06463922 study medication at the beginning 
of each cycle. The number of tablets returned by the patient at the end of the cycle will be 
counted, documented and recorded. Patients will be provided with Patient Diaries. These 
will be detailed in the Investigational Product (IP) manual. 
5.2.9. Drug Storage and Drug Accountability 
PF-06463922 tablets should be stored in accordance with the drug label. Medication should 
be kept in a secured locked area at the study site in accordance with applicable regulatory 
requirements. Patients should be instructed to keep their medication in its original container 
and stored according to the label. Returned medication should be stored separately from 

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medication that is yet to be dispensed. Storage conditions stated in the SRSD (ie, 
Investigator Brochure [IB] will be superseded by the label storage. 
Investigators and site staff are reminded to check temperatures daily (ie, manually or by 
using alarm systems to alert of any excursions) and ensure that the equipment/device(s) are 
working correctly as required for proper storage of investigational products. These may 
include thermometers for both the room storage and refrigerator storage (if applicable). Any 
temperature excursions should be reported to the Sponsor. 
The investigational product(s) must be stored as indicated. Deviations from the storage 
requirements, including any actions taken, must be documented and reported to the Sponsor. 
Once a deviation is identified, the investigational product must be quarantined and not used 
until the Sponsor provides documentation of permission to use the investigational product. 
The temperature of all locations where investigational product (IP) are stored should be 
monitored continuously and verified as appropriate per the site processes, preferably using a 
thermometer that measures minimum and maximum temperatures. Storage temperature 
should be recorded and monitored consistently by the site personnel. If a continuous 
measuring instrument/device is not available, daily temperature (and as applicable, humidity) 
recordings must be taken to ensure compliance with Pfizer requirements and/or site standard 
operating procedures (SOPs), where applicable. If the site has its own SOPs, the most 
conservative standard will be applied, so that Pfizer requirements are always met. 
Midazolam (Phase 1 only) should be stored according to the label. 
The probe drugs used in the DDI and Holter monitoring study should be stored according to 
the label. 
5.2.10. Temperature Excursions 
For any study drugs supplied by Pfizer (ie, PF-06463922 and crizotinib, when applicable), if 
a temperature excursion occurs, the site should immediately contact their study monitor to 
alert them and escalate to Pfizer for evaluation and disposition. Once a deviation is 
identified, the investigational product must be quarantined and not used until the Sponsor 
provides documentation of permission to use the investigational product. When reporting an 
excursion, the following information, at a minimum, should be included: 
• Protocol Number; 
• Site Number; 
• Length of Excursion; 
• Minimum/Maximum Temperatures for the Excursion; 
• Impacted Container Numbers (if applicable); 

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• Confirmation of whether impacted containers were dispensed/administered to 
patients; 
• Copy of temperature monitoring log. 
The site should not use the supplies until a disposition is received from Pfizer via study 
management. The IP should continue to be stored in its appropriate location pending the 
disposition from Pfizer. If the materials are rejected, Pfizer will initiate a replacement 
shipment to the site. 
At D1 of each cycle visit, and at the end of the treatment study, all unused or partially used 
bottles must be returned by patients to the Investigator and Pfizer will provide instructions as 
to disposition of any unused investigational product. If Pfizer authorizes destruction at the 
study site, the investigator must ensure that the materials are destroyed in compliance with 
applicable environmental regulations, institutional policy, and any special instructions 
provided by Pfizer (if applicable). Destruction must be adequately documented. 
5.3. Concomitant Treatments 
Concomitant treatment considered necessary for the patient’s well being may be given at 
discretion of the treating physician. 
All concomitant medications, blood products, as well as non drug interventions (eg, 
paracentesis) received by patients from screening until the end of study visit will be recorded 
on the CRF. All concomitant medications must be approved by the Sponsor at study entry. 
5.3.1. Concomitant Medications (Additionally, refer to Section 5.3.1.1 for Concomitant 
Medications specific to patients participating in the DDI and Holter Monitoring study) 
-In vitro studies have demonstrated that CYP3A, and UGT1A4 are primarily involved in the 
metabolism of PF-06463922, with additional minor contributions from CYP2C19 and 
CYP2C8. Inhibition or induction of the above enzymes may result in potential alteration of 
PF-06463922 systemic exposure. 
Initial in vitro assessment for inhibition and induction drug-drug interaction potential 
indicated that PF-06463922 is a time-dependent inhibitor of CYP3A and also an inducer of 
CYP3A and CYP2B6. At substantially higher concentrations than those observed clinically, 
PF-06463922 also inhibited CYP2C9 in vitro studies. 
To protect patient safety, the following cautions are provided: 
• PF-06463922 metabolism may be inhibited by strong CYP3A inhibitors leading to a 
potential increase in PF-06463922 toxicities. 

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• Coadministration of strong CYP3A inhibitors (eg, boceprevir, cobicistat, 
clarithromycin, conivaptan, diltiazem, idelalisib, indinavir, itraconazole, 
ketoconazole, lopinavir, mibefradil, nefazodone, nelfinavir, posaconazole, ritonavir, 
saquinavir, telaprevir, telithromycin, troleandomycin, voriconazole, grapefruit juice 
or grapefruit/grapefruit-related citrus fruits [eg, Seville oranges, pomelos]) is not 
recommended and alternate medications should be considered. If the concomitant use 
of the strong CYP3A inhibitor cannot be avoided, reduce the starting dose of 
PF-06463922 from 100 mg orally once daily to 75 mg orally once daily. In patients 
who have had a dose reduction to 75 mg orally once daily due to adverse reactions 
and who initiate a strong CYP3A inhibitor, reduce the PF-06463922 dose to 50 mg 
orally once daily. The patient should be closely monitored for safety and reduction of 
the lorlatinib dose if necessary. 
• Use of strong CYP3A inducers with PF-06463922 is contraindicated. 
PF-06463922 metabolism may be induced when taking strong CYP3A inducers (eg, 
carbamazepine, enzalutamide, mitotane, phenytoin, rifampin, St. John’s 
Wort) resulting in reduced plasma concentrations. Furthermore, when PF-06463922 
was coadministered with rifampin (Study B7461011), increases in AST and ALT 
were noted. Discontinue strong CYP3A inducers for 3 plasma half-lives of the strong 
CYP3A inducer prior to initiating PF-06463922 and until study treatment 
discontinuation. In addition, use with moderate CYP3A inducers should be avoided 
due to the potential reduction in PF-06463922 exposure. 
• PF-06463922 inhibits CYP2C9 (in vitro), so concurrent use of drugs that are 
CYP2C9 substrates with narrow therapeutic indices, such as warfarin, phenytoin or 
celecoxib, may have increased effect. Concomitant CYP2C9 substrates should be 
used with caution, as the net clinical effect of PF-06463922 on CYP2C9 is currently 
being investigated. 
• PF-06463922 induces CYP2B6 (in vitro) so concurrent use of drugs that are 
CYP2B6 substrates, such as bupropion and efavirenz, may have less effect. 
Concomitant CYP2B6 substrates should be used with caution, as the net clinical 
effect of PF-06463922 on CYP2B6 is currently being investigated. 
PF-06463922 induces CYP3A (in vivo) which may lead to a decreased effect of 
concurrently used CYP3A substrates. Coadministration of PF-06463922 with 
CYP3A substrates with a narrow therapeutic index (NTI) such as alfentanil, fentanyl 
(including transdermal patch), astemizole*, cisapride*, cyclosporine, 
dihydroergotamine, ergotamine, pimozide, quinidine, sirolimus, tacrolimus, 
terfenadine* (*withdrawn from US market) is not permitted at study entry. However 
if it is absolutely necessary to use, sponsor approval is required and the dose of the 
CYP3A substrate may need to be increased. The NTI CYP3A substrate should be 
started only after at least 14 days of continuous PF-06463922 dosing. If there is a 
change in the PF-06463922 dosing regimen such as a dosing interruption or dose 
reduction, the administration of the NTI CYP3A substrate should be stopped and 
resumed at a readjusted dose only after at least 14 days of resumed PF-06463922 
dosing. 

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• PF-06463922 inhibits P-gp (in vitro) so concurrent use of drugs which are P-gp 
substrates with a narrow therapeutic index may have increased effect. The concurrent 
use of drugs which are P-gp substrates with narrow therapeutic index, such as digoxin 
is not permitted at study entry. The use of these drugs during the study is not 
recommended and alternate medications should be considered. If absolutely 
necessary to use during the study, it should be initiated following sponsor approval, 
and be used then with caution. The net clinical effect of PF-06463922 on P-gp is 
currently being investigated. 
5.3.1.1. Concomitant Medications for Patients participating in the DDI/Holter 
Monitoring Study 
In vitro studies in human hepatocytes indicate PF-06463922 may induce the metabolic 
enzyme CYP2B6 that could in turn lead to decreased exposure of drugs that are metabolized 
by CYP2B6. In addition, the in vitro observation that PF-06463922 also induces the 
metabolic enzyme CYP3A was confirmed clinically in a DDI evaluation with midazolam in 
the Phase I portion of this study. For evaluation of the interaction potential of PF-06463922, 
the following concomitant medications should not be used based on assignment of drug 
probe. 
1. CYP2B6: for the DDI evaluation with buproprion, aCYP2B6 probe substrate, patients 
should not be taking any moderate/strong inhibitors or inducers of CYP2B6 within 
2 weeks of the lead-In probe substrate dosing and until the DDI assessment portion is 
completed on Day 15 of Cycle 1. Refer to the buproprion product insert for complete 
information on contraindications. 
2. CYP2C9: for the DDI evaluation with tolbutamide, a CYP2C9 probe substrate, 
patients should not be taking any moderate/strong inhibitors or inducers of 
CYP2C9 within 2 weeks of the leadIn probe substrate dosing and until the DDI 
assessment portion is completed on Day 15 of Cycle 1. Please refer to the 
tolbutamide product insert for complete information on use and contraindications. 
3. UGTs: for the DDI evaluation with acetaminophen, a UGT probe substrate, patients 
should not be taking any moderate/strong inhibitors or inducers of UGTs within 
2 weeks of the lead-In probe substrate dosing and until DDI assessment portion is 
completed on Day 15 of Cycle 1. Refer to acetaminophen product insert for complete 
information. 
4. P-gp: for the DDI evaluation with fexofenadine, a probe substrate for P-gp, patients 
should not be taking any moderate/strong inhibitors or inducers of P-gp within 
2 weeks of the lead-In probe substrate dosing and until DDI assessment portion is 
completed on Day 15 of Cycle 1. Refer to fexofenadine product insert for complete 
information. 

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5. All subjects with a history of risk factors for QT prolongation or torsades de pointes 
(eg, organic heart disease, congestive heart failure, hypokalemia, hypomagnesemia, 
congenital long QT syndrome, myocardial ischemia or infarction) will be excluded 
from this cohort. 
5.3.2. Other Anti-Tumor or Experimental Drugs 
No additional systemic anti-tumor therapy will be permitted while patients are receiving a 
study therapy. Additionally, the concurrent use of select herbal supplements is not permitted. 
Bisphosphonate therapy for metastatic bone disease is permitted. Bisphosphonate therapy 
should be given as per local medical practice. 
Palliative radiotherapy on study is permitted for the treatment of painful bony lesions 
providing the lesions were known at the time of study entry and the investigator clearly 
indicates that the need for palliative radiotherapy is not indicative of disease progression. In 
view of the current lack of data about the interaction of PF-06463922 with radiotherapy, 
PF-06463922 treatment should be interrupted during palliative radiotherapy, stopping 1 day 
before and resuming treatment after recovery from acute radiation toxicities to baseline. 
5.3.2.1. Hematopoietic Growth Factors 
Primary prophylactic use of granulocyte-colony stimulating factors is not permitted during 
the first cycle but they may be used to treat treatment emergent neutropenia as indicated by 
the current American Society of Clinical Oncology (ASCO) guidelines. 
If approved and available for use per country regulations, erythropoietin may be used at the 
investigator’s discretion for the supportive treatment of anemia. 
5.3.2.2. Anti-Diarrheal, Anti-Emetic, and Acid-Reducing Therapy 
In Phase 1 primary prophylaxis of diarrhea, nausea and vomiting is not permitted in the first 
cycle while assessing DLTs. Primary prophylaxis in subsequent cycles is at the 
investigator’s discretion. 
The choice of the prophylactic drug is up to the investigator with Sponsor approval and 
assuming the drug is not included in the Concomitant section, as well as the duration of 
treatment assuming there is no known or expected drug-drug interaction. If so it must be 
approved by the Sponsor. 
A study to assess the impact of PF-06463922 coadministration with proton-pump inhibitiors 
(PPIs) (eg, lansoprazole [Prevacid®], rabeprazole [Aciphex®], pantoprazole [Protonix®], 
and esomeprazole [Nexium®]) was conducted during the ongoing Phase 2 portion of the 
study. After review of the study results, the observed effect of PPIs on 
PF-06463922 exposure was minor, and not clinically significant. As a result, there is no 
restriction on the use of PPIs (or H2-antagonists, or locally-acting antacids) used 
concomitantly with PF-0646922. Further details of this study can be found in the 
Investigator Drug Brochure. 

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5.3.2.3. 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 section. 
5.3.2.4. Cutaneous Toxicity Therapy 
Prompt medical intervention is recommended at the first sign of appearance of cutaneous 
toxicity including topical or oral corticosteroids if required according to investigator’s 
judgment, assuming there is no known or expected drug-drug interaction and assuming the 
drug is not included in the Concomitant section. 
5.3.2.5. Testosterone Replacement 
Testosterone replacement therapy is only allowed in the presence of signs and symptoms 
clearly attributable to hypogonadism in consultation with an endocrinologist, who should 
also exclude any potential confounding effects of elevated prolactin and/or estradiol, or a 
significant recent change in corticosteroid dose, before doing so. 
5.3.2.6. Lipid-Lowering Therapy 
Treatment with a statin is recommended at the first signs of elevated (Grade 1) cholesterol 
and/or triglycerides. Clinically, PF-06463922 has limited data, but it is a moderate inducer 
of CYP3A. Combined with the in vitro data that PF-06463922 can itself be metabolized by 
CYP3A, 2C19, 2C8 and UGT1A as well as inhibit 2C9 and induce 2B6, the choice and dose 
of statin should be considered carefully. 
Statins can be metabolized by CYP enzymes affected by PF-06463922, or affect the CYP 
enzymes that metabolize PF-06463922 (Table 14). Therefore, the statins with the least 
involvement of the CYP450 enzyme systems to use concomitantly with PF-06463922 would 
be pitavastatin or pravastatin followed by rosuvastatin. However, clinical drug-drug 
interactions have not been formally studied with PF-06463922, so careful monitoring is 
advised. 
Similarly, if hypertriglyceridemia requires treatment, the drugs with the least involvement of 
the CYP450 enzyme systems to use concomitantly with PF-06463922 would be fenofibrate 
or fish oils followed by nicotinic acid (Table 15). Again, clinical drug-drug interactions have 
not been formally studied with PF-06463922, so careful monitoring is advised. 

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Table 14. Pharmacokinetic Properties of Statins 
 
Generic 
name (or 
equivalent) 
Pitavastatin 
Pravastatin 
Rosuvastatin 
Atorvastatin 
Simvastatin 
Lovastatin 
Fluvastatin 
Metabolism† 
++ 
+ 
+ 
+++ 
+++ 
+++ 
+++ 
Metabolizing 
(2C9) 
(3A4) 
2C9 (2C19) 
3A4 (2C8) 
3A4 2C8 
3A4 2C8? 
2C9 
CYP 
enzymes (of 
lactone or 
acid form) 
Inhibitor of 
+ 
+ 
+ 
+ 
+ 
CYP3A4‡ 
Inhibitor of 
(+) 
+ 
CYP2C9‡ 
Triglyceride 
22-30%** 
11-14%* 
17%* 
14-19%* 
10-14%* 
13%* 
0-5%*** 
lowering 
effect 
Parentheses indicate minor significance. 
†Three plus signs indicate extensively metabolized, and 1 plus sign indicates limited metabolism, eliminated mainly 
unchanged. 
‡A plus sign indicates yes, and a minus sign indicates no. 
* Baseline TG 100-200 mg/dL; Effect of Statins vs Placebo on Triglyceride Levels in 10 Primary and Secondary 
Placebo-Controlled Outcome Trials. http://www.medscape.org/viewarticle/589010. 
** Baseline TG ≥150 mg/dL; Cardiovascular Drug Reviews. 2003; 21(3): 199–215. 
*** Am J Cardiol 2004;93:31–39. 
adapted from Clin Pharmacol Ther 2006;80:565-81. 
 
Table 15. Pharmacokinetic Properties of Lipid Lowering Agents 
 
Fibric Acids 
Fish Oils 
 
Generic Name (or 
equivalent) 
Nicotinic Acid 
Gemfibrozil 
Fenofibrate 
Ethyl esters of 
omega-3 fatty 
acids 
Metabolism‡ 
- 
- 
- 
- 
Metabolizing CYP enzymes 
- 
- 
- 
- 
(of lactone or acid form)‡ 
Inhibitor of CYP3A4‡ 
- 
- 
- 
- 
Inhibitor of CYP2C9‡ 
- 
+++ 
++ 
- 
Inhibitor of CYP2C19‡ 
- 
++ 
+ 
- 
Inhibitor of CYP1A2‡ 
- 
+ 
- 
- 
Triglyceride lowering effect 
(TG ≥150 mg/dL) 
20-50%* 
20-50%* 
36% - 55%a 
45%a 
Drug Interactions 
Caution should be used 
when prescribing niacin 
with statins 
Concomitant 
administration 
with statins is 
contraindicated 
May increase 
exposure to 
pravastatin and its 
metabolite 
(13-29%) when 
used concomitantly 
‡A plus sign indicates yes, and a minus sign indicates no. 
a primary hypertriglyceridemia – severe hypertriglyceridemia (Baseline TG levels >500 mg/dL). 
b PI, 4/2015. 
c PI, 11/2014. 
d PI, 12/2014. 
e PI, 05/2014. 
* NCEP-ATP III, 2001. 

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5.3.3. Supportive Care 
Palliative and supportive care for disease-related symptoms may be administered at the 
Investigator’s discretion and according to available American Society of Clinical Oncology 
(ASCO) guidelines. 
5.3.4. Surgery 
Caution is advised on theoretical grounds for any surgical procedures during the study. The 
appropriate interval of time between surgery and PF-06463922 required to minimize the risk 
of impaired wound healing and bleeding has not been determined. Stopping PF-06463922 is 
recommended at least 2 days prior to surgery. Postoperatively, the decision to reinitiate 
PF-06463922 treatment should be based on a clinical assessment of satisfactory wound 
healing and recovery from surgery. 
6. STUDY PROCEDURES 
Section 5 includes Study Procedures for PF-06463922 only. When applicable, patients who 
receive crizotinib following PF-06463922 should follow the required Study Procedures as 
outlined in Appendix 11. 
6.1. Screening 
For screening procedures, see Schedule of Activities (Table 3, Table 4, Table 5) and 
Assessments section. For the Japanese patient-only LIC, refer to Appendix 9 for the 
schedule of required assessments. For patients in the DDI and Holter monitoring study, refer 
to Table 6. 
6.1.1. Archival Tumor Tissue 
These samples are mandatory for all patients enrolled in the study. Formalin fixed, paraffin 
embedded (FFPE) tissue block(s) from initial diagnosis that contain sufficient tissue to 
generate at least 6 (preferably 12), 5-micron thick unstained slides will be collected. If no 
FFPE block is available, then at least 6 (preferably 12) unbaked, 5-micron thick unstained 
slides containing FFPE tumor tissue must be provided. The archived tumor tissue may be 
obtained and analyzed outside the 28 day screening window. In cases where archived tumor 
tissue is not available, a de novo biopsy should be obtained for this purpose. 
Samples will be sent to the Sponsor-designated central laboratories for assessment of 
biomarkers potentially associated with sensitivity and/or resistance to 
PF-06463922 (eg, ALK mutations, mutations/copy number variation of various genes, 
expression and/or phosphorylation of various proteins, etc); for ROS1+ NSCLC patients 
samples will be sent to the Sponsor-designated central laboratory for ROS1 status 
confirmation. Tissue samples from all patients will be used for additional biomarker 
analyses. Details for handling of these samples including processing, storage, and shipment 
will be provided in the Study Manual. 

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6.1.2. De Novo Tumor Biopsy 
These samples will be mandatory for all patients enrolled in the Phase 2 (and in Phase 1 if 
archival tumor tissue is not available), unless it is considered to pose a safety risk to the 
patient, in the opinion of the Investigator, and only after discussion with the Sponsor; please 
refer to Section 7.3 for further guidance. For patients who are treatment naïve at Screening 
(ie, no previous systemic therapy in the metastatic disease setting), a de novo tumor biopsy is 
not required if a previous tumor biopsy was performed within 4 months of first 
PF-06463922 dose. When applicable, this de novo biopsy must be taken no more than 
28 days prior to starting study treatment. The de novo biopsy will consist of an incisional or 
excisional biopsy, or a core needle biopsy, of a primary or metastatic lesion. Pleural 
effusions (PE) cell pellets may substitute for a tumor core biopsy, as appropriate. Fine 
needle aspiration (FNA) samples (2-3 pathes prepared as FFPE cell block as per institutional 
practice) are not preferred and should only be performed in the event a biopsy or pleural 
effusion cell pellet is not safe or feasible. If local/country regulations do not allow for tissue 
block to be submitted, 5-micron FFPE tumor tissue slides (at least 12 slides) are acceptable. 
The tumor tissue will be processed as specified in the Laboratory Manual. 
Additional, optional de novo tumor specimen collection at screening (Phase 1) and at the 
time of progression (Phase 1 and Phase 2) is strongly encouraged from all patients. If 
present, pleural effusion (PE) cell pellet may substitute for tumor core biopsy. As noted 
above, a de novo biopsy should be obtained in cases where archived tumor tissue is not 
available. 
6.2. Study Period 
For treatment period procedures, see Schedule of Activities (Table 2, Table 3, Table 4, 
Table 5) and Assessments section. For the Japanese patient-only LIC, refer to 
Appendix 9 for the schedule of required assessments. For patients participating in the DDI 
and Holter monitoring study refer to Table 6. 
A reduced schedule of assessments (Table 1) will be followed for all patients after 
Amendment 8 is approved locally. Sufficient study medication for 2 cycles of treatment will 
be dispensed at each clinic visit. The Investigator is responsible for informing the patient to 
contact the clinical site in case of any adverse events. Laboratory tests will be performed as 
per local practice; the results will not be collected, however the copy of the laboratory test 
results must be retained in the patient’s file at the clinical site for documentation purposes. 
The pregnancy test should be performed at the clinical site’s local laboratory. Where that is 
not possible, patients will provide the laboratory test results carried out at a non-clinical site 
laboratory, eg, to the site staff by telephone, and bring a copy of the laboratory test results at 
the next cycle visit. The copy of the pregnacy test results must be retained in the patient’s 
file at the clinical site for documentation purposes. The patient may be contacted by phone 
to confirm contraception is still appropriate per the protocol. 

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6.3. Follow-up Visit 
For follow-up procedures, see Schedule of Activities (Table 2, Table 3, Table 4, and Table 5) 
and Assessments section. For the Japanese patient-only LIC, refer to Appendix 9 for the 
schedule of required assessments. For patients participating in the DDI and Holter 
monitoring study refer to Table 6. 
At least 28 days, and no more than 35 days after discontinuation of treatment patients will 
return to the site to undergo assessment for resolution of any treatment-related toxicity, and 
pregnancy test for females. Patients continuing to experience toxicity at this point following 
discontinuation of treatment will continue to be followed at least every 4 weeks until 
resolution or determination, in the clinical judgment of the Investigator, that no further 
improvement is expected. Patients discontinuing treatment for progression of disease or for 
reasons other than progression of disease will enter the follow-up phase. -The survival 
follow-up will be performed every 2 months and will include also the collection of 
information on subsequent anticancer therapies (telephone contact is acceptable). For 
patients who receive crizotinib following treatment with PF-06463922, a follow-up visit will 
not be required until discontinuation of crizotinib as outlined in Appendix 11. 
6.4. Patient Withdrawal 
Patients may withdraw from treatment at any time at their own request, or they may be 
withdrawn at the discretion of the investigator or Sponsor for safety or behavioral reasons, or 
the inability of the patient to comply with the protocol required schedule of study visits or 
procedures at a given study site. 
Reasons for withdrawal of study treatment may include: 
• Objective disease progression according to modified RECIST v1.1 unless in the 
investigator’s opinion the patient is still deriving clinical benefit; 
• Global deterioration of health status requiring discontinuation; 
• Unacceptable toxicity; 
• Pregnancy; 
• Significant protocol violation; 
• Lost to follow-up; 
• Patient refused further treatment; 
• Study terminated by Sponsor; 
• Death. 

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Reasons for withdrawal from study follow-up may include: 
• Completed study follow-up; 
• Study terminated by Sponsor; 
• Lost to follow-up; 
• Refusal for further follow-up for survival; 
• Death. 
If a patient does not return for a scheduled visit, every effort should be made to contact the 
patient by telephone etc and attempted contacts should be recorded in the patient’s medical 
record. In any circumstance, every effort should be made to document patient outcome, if 
possible. The investigator should inquire about the reason for withdrawal, request the patient 
to return all unused investigational product(s), request the patient to return for a final visit, if 
applicable, and follow-up with the patient regarding any unresolved adverse events (AEs). 
If the patient refuses further visits, the patient should continue to be followed for survival (if 
survival is a secondary endpoint) unless the patient withdraws consent for disclosure of 
future information or for further contact. In this case, 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 
Required assessments for all patients except those in the Japanese patient-only LIC or those 
patients receiving crizotinib following PF-06463922 are described in the Schedule of 
Activities tables (Table 2, Table 3, Table 4, Table 5, and Table 6). Refer to Appendix 9 for 
the schedule of required assessments for patients in the Japanese patient-only LIC. Refer to 
Appendix 11 for the required assessments for patients receiving crizotinib following 
PF-06463922. For patients participating in the DDI and Holter monitoring study refer to 
Table 6. 
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 can not be performed the 
investigator will document the reason for this and any corrective and preventive actions 
which he/she has taken to ensure that normal processes are adhered to as soon as possible. 
The study team will be informed of these incidents in a timely fashion. 
Upon approval of Amendment 8, Schedule of Activities will be reduced as indicated in 
Table 1. 

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7.1. Safety Assessment 
Safety assessments will include collection of AEs, SAEs, vital signs and physical 
examination, Mini Mental State Exam (MMSE) [Phase 1 only; no longer required per 
Amendment 6] ECG (12-lead), echocardiogram or Multi Gated Acquisition Scan (MUGA), 
laboratory assessments, including pregnancy tests and verification of concurrent medications. 
Additionally, neurological examinations will be included in at least 12 Phase 1 patients. In 
Phase 2, assessments of cognitive, mood, and suicidal ideation and behavior will be 
collected. 
7.1.1. Pregnancy Testing 
For female patients of childbearing potential, a serum or urine pregnancy test, with 
sensitivity of at least 25 mIU/mL, will be performed on two occasions prior to starting study 
therapy - once at the start of screening and once at the baseline visit, immediately before 
investigational product administration. Following a negative pregnancy result at screening, 
appropriate contraception must be commenced and another negative pregnancy test will then 
be required at the baseline visit before the patient may receive the investigational product. 
Pregnancy tests will also be routinely repeated at each cycle during the active treatment 
period, at the end of study therapy, at least 28 days and no more than 35 days after 
discontinuation of treatment, and additionally whenever one menstrual cycle is missed or 
when potential pregnancy is otherwise suspected. In the case of a positive hCG test, the 
patient will be withdrawn from study medication but may remain in the study. 
Additional pregnancy tests may also be undertaken if requested by Institutional Review 
Boards/Ethics Committees (IRBs/IECs) or if required by local regulations. 
7.1.2. Adverse Events 
Assessment of adverse events will include the type, incidence, severity (graded by the 
National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] 
version 4.03), seriousness, and relatedness. 
Adverse events that occur during the study, including baseline signs and symptoms, will be 
recorded on the adverse events CRF page. 
7.1.3. Laboratory Safety Assessment 
Hematology and blood chemistry will be drawn at the time points described in the Schedule 
of Activities (and in Appendix 1 and Appendix 2) and analyzed at local laboratories. 
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 screening only blood pressure and pulse rate to be 
recorded in sitting position after approximately 5 minutes of rest. 

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7.1.5. (12-Lead) Electrocardiograms 
Electrocardiogram (ECG): Triplicate 12-lead (with a 10-second rhythm strip) tracing will be 
used for all ECGs. It is preferable that the machine used has a capacity to calculate the 
standard intervals automatically. At each time point (see the Schedule of Activities), 
3 consecutive ECGs will be performed at approximately 2 minutes apart to determine the 
mean QTc interval. If the mean QTc is prolonged (>500 msec, ie, CTCAE Grade 3), then 
the ECGs should be re-evaluated by a qualified person at the site for confirmation as soon as 
the finding is made, including verification that the machine reading is accurate. If manual 
reading verifies a QTc of >500 msec, immediate correction for reversible causes (including 
electrolyte abnormalities, hypoxia and concomitant medications for drugs with the potential 
to prolong the QTc interval) should be performed. In addition, repeat ECGs should be 
immediately performed hourly for at least 3 hours until the QTc interval falls below 
500 msec. If QTc interval reverts to less than 500 msec, and in the judgment of 
Investigator(s) and Sponsor is determined to be due to cause(s) other than study drug, 
treatment may be continued with regular ECG monitoring. If in that timeframe the QTc 
intervals rise above 500 msec the study drug will be held until the QTc interval decreases to 
500 msec. Patients will then re-start the study drug at the next lowest dose level. If the 
QTc interval has still not decreased to <500 msec after 2-weeks, or if at any time a patient 
has a QTc interval >515 msec or becomes symptomatic, the patient will be removed from the 
study. Additional triplicate ECGs may be performed as clinically indicated. 
Prior to concluding that an episode of prolongation of the QTc interval is due to study drug, 
thorough consideration should be given to potential precipitating factors (eg, change in 
patient clinical condition, effect of concurrent medication, electrolyte disturbance) and 
possible evaluation by specialist. 
If a patient experiences asymptomatic or symptomatic first-degree or second-degree PR 
prolongation, or third-degree AV block,refer to Section 5.2.7. 
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 an ECG 
and PK sample are scheduled at the same time, the ECG must be carried out before each PK 
sample drawing such that the PK sample is collected at the nominal time (ie, the timing of the 
PK collections over rides the timing of the ECG collections). 
7.1.6. Transthoracic echocardiogram (TTE) (France and Germany only) 
As requested by Health Authorities in Germany and France, a TTE will be performed for 
patients in France and Germany at least every 6 months (±2 weeks) during treatment, and 
only at the End of Treatment visit if the previous assessment was >1 month. Pulmonary 
arterial pressure (PAP) will be assessed. Additional monitoring should be done as follows: 
• A prompt TTE in the event of symptoms or signs suggesting pulmonary arterial 
hypertension (PAH) and all other explorations pursuant to PAH diagnosis guidelines. 

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• Should PAH occur during treatment, following multidisciplinary discussions 
involving a PAH specialist (cardiologist or pulmonologist), consider dose reductions 
or even permanently discontinuing lorlatinib in the absence of haemodynamic and 
clinical recovery. 
7.1.7. Holter Monitoring (DDI and Holter Monitoring study only) 
In order to characterize the effects of PF-06463922 on ECG endpoints, continuous Holter 
telemetry of patients will be used to evaluate the effect of PF-06463922 on the PR interval by 
comparing the patients pre-drug baseline with PR interval observations associated with 
exposure of PF-06463922 following a single dose and at steady state. Twenty-four Holter 
monitoring will be conducted on Day -1 through Cycle 1 Day 1 and again on Cycle 1 
Day 14. On Day -1, the 24-hour Holter monitoring will begin approximately 24 hours after 
probe substrate administration on Day -2. On Cycle 1 Day 14, 24-hour Holter monitoring 
will begin immediately prior to PF-06463922 administration. Refer to Table 6 of the 
Schedule of Activities. 
7.1.8. Echocardiogram and Multi Gated Acquisition Scan (MUGA) 
In order to monitor potential left ventricular ejection fraction dysfunction, an echocardiogram 
or MUGA will be performed at the time points described in the Schedule of Activities. The 
same method should be used at each time point. 
7.1.9. Mini Mental State Exam (MMSE) (Phase 1 Only; no longer required per 
Amendment 6) 
The Mini Mental State Exam (MMSE) is a tool that can be used to systematically and 
thoroughly assess mental status.37 The standard version of the MMSE is a 30 item 
questionnaire that tests 5 areas of cognitive function: orientation, registration, attention and 
calculation, recall and language. The maximium score is 30. A score of 23 or lower is 
indicative of cognitive impairment. The MMSE takes 5-10 minutes to adminster. The 
MMSE is effective as a screening instrument to separate patients with cognitive impairment 
fromthose without it. In addition, when used repeatedly the instrument is able to measure 
changes in cognitive status over the study treatment period. It has been used in the advanced 
cancer setting.38 
This screening assessment will not substitute the clinical assessment done for Adverse Event 
reporting. Should the sum of the rating score after all questions are completed be less than 
24, the investigator should assess if there are clinical signs that fulfill the adverse event (AE) 
reporting criteria (Section 8.8 Severity Assessment). 
7.1.10. Neurological Examination (Phase 1 Only) 
A neurological examination by a licensed neurologist will be performed in at least 
12 Phase 1 patients at baseline and, if clinically indicated, at any time point thereafter. 

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7.1.11. Assessment of Cognitive Function (Phase 2 Only) 
In order to assess cognitive function and any changes associated with 
PF-06463922 adminsitration, a computerized test (using laptops provided to sites by 
Cogstate) will be administered to patients at the time-points described in the Schedule of 
Activities. The test will be administered by a qualified site personnel and will take 
approximately 15-20 minutes to complete. This test is developed and validated by 
Cogstate.44 This test is a 5-part battery test consisting of the following: 
The International Shopping List Task (Verbal Learning) 
The International Shopping List task is a measure of verbal learning and uses a 
well-validated list-learning paradigm. The task is administered using a computer. High 
frequencies, high imagery, concrete nouns (items from a shopping list) are read to the patient 
by the qualified site personnel at the rate of one word every 2 seconds. Once all 12 words 
have been read, the patient is asked to recall as many of the words as he/she can as quickly as 
possible. The site qualified personnel uses a mouse or stylus to mark the words recalled by 
the patient on the computer screen. When the patient can recall no more words, the same list 
is read a second time. The qualified site personnel records the words recalled by the patient 
on this trial. This is then repeated a third time. The delayed recall condition requires the 
patient to recall the words from the list 10-30 minutes later without having the list read again. 
The software measures the number of correct responses as recorded by the qualified site 
personnel. Duration of Task: approx. 5 minutes. 
Detection (Psychomotor Function) 
The Detection task is a measure of psychomotor function and uses a well-validated simple 
reaction time paradigm with playing card stimuli. In this task, the playing cards all depict the 
same joker. The patient is asked to press the Yes key as soon as the card in the center of the 
screen turns face up. The software measures the speed and accuracy of each 
response. Duration of Task: approx. 2 minutes. 
Identification (Attention) 
The Identification task is a measure of visual attention and uses a well-validated choice 
reaction time paradigm with playing card stimuli. In this task, the playing cards are all either 
red or black jokers. The patient is asked whether the card displayed in the center of the 
screen is red. The patient responds by pressing the Yes key when the joker card is red and 
No when it is black. The software measures the speed and accuracy of each response. 
Duration of Task: approx. 2 minutes. 
One Back (Working Memory) 
The One Back task is a measure of working memory and uses a well-validated n-back 
paradigm with playing card stimuli. In this task, the playing cards are identical to those 
found in a standard deck of 52 playing cards (without the joker cards). The patient is asked 
whether the card displayed in the center of the screen is the same as the card presented 
immediately previously. The patient responds by pressing the Yes or No key. Because no 
card has been presented yet on the first trial, a correct first response is always No. The 
software measures the speed and accuracy of each response. Duration of Task: approx. 
3 minutes. 

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International Shopping List Test (Delayed Recall) 
The delayed recall condition requires the patient to recall the words from the list 
15-30 minutes later without having the list read again. During the recognition condition, the 
qualified site personnel reads a shopping list item that may or may not have been on the 
original list and the patient has to respond either affirmatively (if the item was on the original 
list) or negatively (if it was not). The software measures the number of correct responses. 
Duration of Task: approx. 5 minutes. 
7.1.12. Assessment of Mood (Phase 2 Only) 
An assessment of mood will be administered to patients via the Beck Depression Inventory-II 
(BDI-II) scale at the timepoints described in the Schedule of Activities. This is a 21 item 
self-report scale, with each item rated by patients on a 4 point scale (ranging from 0-3.). The 
scale includes items capturing mood, (loss of pleasure, sadness, irritability), suicidal ideation, 
and cognitive signs (punitive thoughts, self- criticism, self-dislike, pessimism poor 
concentration) as well as somatic signs (appetite, sleep, fatigue, libido). 
7.1.13. Assessment of Suicidal Ideation and Behavior (Phase 2 Only) 
To assess suicidal ideation behaviors, the Columbia Suicide Severity Rating 
Scale43 (C-SSRS) will be administered to patients at the timepoints described in the Schedule 
of Activities. The C-SSRS is a unique, simple and short method of assessing both behavior 
and ideation that tracks all suicidal events and provides a summary of suicidality. It assesses 
the lethality of attempts and other features of ideation (frequency, duration, controllability, 
reasons for ideation and deterrents), all of which are significantly predictive of completed 
suicide. This paper based assessment will be provided by Cogstate. 
7.2. Pharmacokinetics Assessments 
For patients participating in the DDI and Holter monitoring study, refer to Section 7.2.8. 
7.2.1. Blood for PK Analysis of PF-06463922 
Blood samples (4 mL whole blood to provide at least 2 ml of plasma) will be collected for 
PK analysis of PF-06463922 as outlined in the Schedule of Activities (Table 3 and Table 5). 
All patients in Phase 1 and 10 Non-Japanese and 3 Japanese (non-LIC) patients in 
Phase 2 will have full plasma PK sampling. Blood samples will be collected on Day (-7), in 
Cycle 1 on Day 1, Day 8, and Day 15 and Day 1 of Cycles 2-5. Additionally, in 
Phase 2 only, for Day 1 of Cycle 6 and Day 1 of every other cycle (ie, Cycle 6, Cycle 8, etc.). 
For patients in Phase 2 who undergo sparse plasma PK sampling, blood samples will be 
collected at pre-dose on Day 1 of Cycles 1-5 (Table 5) and predose on Day 1 of every other 
cycle beginning with Cycle 6 (ie, Cycle 6, Cycle 8, etc). 
For patients who participate in the MDZ interaction sub-study (Table 3), blood samples for 
PF-06463922 PK will be collected on Day 1, Day 8, and Day 15 in Cycle 1. For 
Cycles 2-5, PK samples will also be collected on Day 1. 

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For patients who participate in the food effect sub-study (Table 3), blood samples for 
PF-06463922 PK will be collected on Day -7, Day 1, Day 8, and Day 15 in Cycle 1. For 
Cycles 2-5, PK samples will also be collected on Day 1. 
PK sampling schedule may be modified based on emerging PK data. In addition to samples 
collected at the scheduled times, an additional blood sample should be collected from 
patients experiencing unexpected and/or serious AEs and the date and time documented in 
the CRF. 
All efforts will be made to obtain the pharmacokinetic samples at the scheduled nominal time 
relative to dosing. However, 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 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 for PF-06463922 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. 
7.2.2. Urine for PK Analysis of PF-06463922 
In the Phase 1 food effect and midazolam interaction cohort, urine samples will be collected 
for 24 hours after PF-06463922 dosing on Cycle 1 Day 15 to measure 
PF-06463922 concentrations, and thereby determine the renal elimination of 
PF-06463922 from the body. Metabolites of PF-06463922 may also be measured in the 
urine samples. Urine will be collected on Cycle 1 Day 15 over the following intervals: 0 to 
4 hours, 4 to 12 hours and 12 to 24 hours post-dose (Table 3). For patients on BID dosing, 
12-24-hour post-dose urine collection is not required. Patients will empty their bladder just 
prior to dosing on Cycle 1 Day 15. 
At the end of each urine collection period, the total volume will be measured and recorded. 
Voided urine should be collected in an amber container and protected form direct light. The 
urine will then be mixed thoroughly and a 20 mL aliquot will be withdrawn for the potential 
measurement of drug concentrations. The sample will be protected from light and frozen at 
approximately -20C. 
7.2.3. Blood for Metabolite Profiling of PF-06463922 
Metabolite profiling will be conducted in the food effect cohort (Phase 1) and in 
10 Non-Japanese patients and 3 Japanese non-LIC patients enrolled in Phase 2. Blood 
samples for metabolite profiling will be collected on Cycle 1 Day 15 (Table 3, Table 5). 
Two (2) mL of blood will be collected at each time point to obtain 1 mL of plasma. 
Details regarding the collection, processing, storage and shipping of the blood samples will 
be provided in the study manual. 

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Once the metabolite profiling samples have been analyzed and the report completed, the 
samples will be disposed. 
7.2.4. CSF for Analysis of PF-06463922 Concentration 
If a patient is required to undergo a lumber puncture while on trial,, an additional ~5 mL 
sample of CSF should be collected for determining PF-06463922 concentrations any time at 
steady state. If a CSF sample is collected, a plasma PK sample should also be collected at 
approximately the same time. Detailed collection procedures will be provided in the 
laboratory manual. 
7.2.5. Blood for PK Analysis of Midazolam 
In the Phase 1 MDZ interaction sub-study, blood samples (2 ml each for 1 ml of plasma) for 
PK analysis of MDZ will be collected after a single oral MDZ dose on Day –7 and 
Cycle 1 Day 15 at the time points specified in the schedule of activities (Table 3). 
7.2.6. Urine Sample for 6 beta-Hydroxycortisol/Cortisol (6-OHC/C) Ratio 
A midstream morning spot urine sample (10 mL) will be colleted into an appropriately 
labeled plastic screw topped collection container prior to dosing in Phase 1 of any drug on 
Day-7, Day 1 of Cycle 1, Day 8 of Cycle 1, Day 15 of Cycle 1 and Day 1 of 
Cycle 2 (Table 3). The urinary 6 beta-hydroxycortisol/cortisol (6-OHC/C) ratio will be 
determined to evaluate CYP3A induction. 
7.2.7. Blood for 4 beta-Hydroxycholesterol/Cholesterol 
Blood samples (3 ml to provide 1.5 ml of plasma) for the analysis of 4-hydroxycholesterol 
and cholesterol will be collected in Phase 1 at pre-dose on Day-7, Cycle 1 Day 1, 
Cycle 1 Day 8, Cycle 1 Day 15 and Cycle 2-5 Day 1 (Table 3). The 
4 beta-hydroxycholesterol/Cholesterol is a new marker thatis being explored for assessing 
CYP3A induction. 
7.2.8. PK for patients participating in the Drug-Drug Interaction and Holter 
Monitoring study 
Refer to Table 6 in the Schedule of Activities. Refer to the study manaual for detailed 
requirements on PK collection, processing and shipping. 
Blood samples (4 mL each) for PF-06463922 full PK sampling will be collected on the 
following days 1) Cycle 1 Day 1 and Cycle 1 Day 15: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, and 
24 hrs post PF-06463922 dose and 2) Day 1 of Cycle 2, Cycle 4, Cycle 6, Cycle 8 and 
Cycle 10: Pre-dose. 
Where required by local regulations and after agreement by the study sponsor, patients may 
be hospitalized for PK sampling. 

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Blood samples (4 mL each) for PF-06463922 metabolite(s) will be collected in all patients on 
Cycle 1 Day 1, and at steady-state on Cycle 1 Day 15 at: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, and 
24 hrs post-PF-06463922 dose (the following day). 
For evaluation of drug-drug interaction, plasma blood samples (3 mL each) for PK Sampling 
for probe substrates will occur on the following days and times: 
a. Day-2 (Lead-in): Pre-dose, 0.5, 1, 2, 3, 4, 6, and 8 and 24 hrs post dose. 
b. Cycle 1 Day 15: Pre-dose, 0.5, 1, 2, 3, 4, 6, and 8 and 24 hrs post dose. 
A single blood sample for genotyping will be collected at baseline to determine the genetic 
status of the major drug metabolizing enzymes and transporters. The K2EDTA 
(ethylenediaminetetraacetic acid) samples will be analyzed in compliance with Pfizer 
standard operating procedures in a CLIA (Clinical Laboratory Improvement Amendments) 
regulated laboratory. 
A 4-mL blood sample will be collected from each subject into a plastic edetic acid (K2EDTA) 
tube on Day -2 and stored for prospective ADME genotyping (drug-metabolizing enzymes 
and transporters only). Immediately after the sample is collected, the tube should be gently 
inverted 10 to 15 times to ensure adequate mixing of the tube contents. Samples are to be 
stored frozen at -20ºC or colder in a secure freezer at the investigative site until shipment in 
batches on dry ice. Unless otherwise specified, samples will be retained for 3 years after the 
end of the study. 
7.3. Pharmacodynamic Assessments 
Biomarker studies on tumor tissue and blood will be carried out to help understand the 
mechanism of action of PF-06463922, as well as identify potential mechanisms of resistance. 
Such results may help in the future development of this drug as a single agent or in 
combination. These analyses may also result in the identification of potential biomarkers of 
response to PF-06463922, ultimately leading to development of a patient selection strategy 
for further clinical investigation. Collection of peripheral blood samples for biomarker 
assessments will be mandatory for all patients; samples should be obtained at the same time 
as PK samples whenever possible. 
Tumor tissue from archived tissue specimens and/or a de novo biopsy (see Section 6.1.1 and 
Section 6.1.2) will be used to analyze candidate DNA, RNA or protein markers for their 
ability to predict or identify those patients who are most likely to benefit from treatment with 
the study drug. Markers that may be analyzed include, but may not be limited to ALK or 
ROS kinase domain mutation. 
De novo tumor core biopsies collection in Phase 2 is mandatory unless it poses a safety risk 
to the patient, in the opinion of the Investigator, and only after discussion with the Sponsor. 
Examples of safety risks may include, but are not limited to: (a) pulmonary metastases deep 
within the thoracic cavity with high probability of bleeding or lung injury; (b) liver 
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every efforts should be made to collect fine needle aspiration (FNA) samples (2-3 pathes 
prepared as FFPE cell block) which are not preferred and should only be performed in the 
event a biopsy or pleural effusion cell pellet are not safe or feasible. 
Table 16 summarizes the biomarker assessments currently planned for the study. Tumor 
specimens (archival tissue and de novo biopsy) will be analyzed for the presence of 
mutations affecting the kinase domain of ALK and/or for ROS1 rearrangment (for the 
patients enrolled in the ROS1+ arm). Additional pathway related markers (eg, EGFR, KIT) 
may be included as preclinical studies or literature reports further elucidate the mechanisms 
of resitance to ALK and/or ROS1 inhibition. Please 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 16. Summary of Biomarker Assessments 
 
Assay 
Source 
Circulating Nucleic Acid mutational analysis of ALK kinase domain 
mutations 
Peripheral blood 
CTC enrichment and/or profiling for ALK or 
ROS1 rearrangement/mutation (Phase 1 only; no longer required) 
Peripheral blood 
Profiling of ALK kinase domain mutations or ROS1 status 
confirmation 
Archival tumor specimen and de 
novo tumor biopsies 
Molecular profiling for mutations, gene copy number variant for 
candidate genes, RNA/miRNA profiling and/or 
expression/phosphorylation for candidate proteins involved in 
possible by-pass mechanisms relevant to sensitivity/resistance to 
treatment 
Archival tumor specimen and de 
novo tumor biopsies 
 
7.4. Tumor Response Assessments 
Tumor assessments will include all known or suspected disease sites. CT scans of Chest 
Abdomen Pelvis [CAP] and MRI of the brain will be performed at screening. Gadolinium 
contrast enhanced MRI must be used to assess CNS lesions with contingent slices of 1 mm 
for lesions 5 mm – 10 mm in size. For CNS lesions measuring between 10 mm and 40 mm 
gadolidium contrast enhanced MRI must be used with contingent slides of 5 mm. For 
patients who are without documented disease progression, CT and MRI scans will continue 
to be done at every 6 weeks 1 week for the first 18 months in Phase 1 and first 30 months in 
Phase 2, and and then every 12 weeks ±1 week thereafter, and responses will be confirmed 
4 weeks later (RECIST v1.1), until documented progression of disease. For patients who 
have documented disease progression, but are still receiving PF-06463922, tumor 
assessments are to be done according to local institutional standard of care. Bone scans (or 
bone MRI if preferred by investigator) will be performed at baseline for all patients 
(regardless of bone involvement) and repeated every 12 weeks on study only if evidence of 
bone metastases are observed at baseline (however, if a patient has bone involvement, 
assessment of those sites via appropriate modality is required every 6 weeks ±1 week up to 
18 months in Phase 1 and 30 months in Phase 2, and then every 12 weeks ±1 week thereafter. 
For all tumor assessments, the same method of assessment at baseline should be used 

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throughout the study. In Phase 2 patients with LM or CM not visualized on baseline MRI, a 
positive CSF cytology will be required at baseline (optional post baseline). Tumor 
assessment should be repeated at the end of treatment visit if more than 6 weeks (more than 
12 weeks beyond 18 months in Phase 1 and 30 months in Phase 2) have passed since the last 
evaluation. For patients enrolled in Phase 2, tumor assessments must continued until 
progression of disease or the start of a new anti-cancer therapy. 
The same imaging technique used to characterize each identified and reported lesion at 
baseline will be employed in the following tumor assessments. 
[18F]-FLT-PET and [18F]-FDG-PET imaging for assessment of functional response may be 
used in addition to but not substitute the required radiology modalities listed above. Positron 
emission tomography (PET) imaging used to explore early signals of anti-tumor activity will 
be collected pre and post PF-06463922. The screening PET study will be used to determine 
evaluable index lesions for each patient. Tumor background ratios (TBR) and development 
of new sites of abnormality will be recorded. 
Results of the PET studies will be scored according to methods developed by the American 
College of Radiology Imaging Network (ACRIN; http://www.acrin.org/petcorelab.html). All 
centers participating in the study will use the same PET methodologies and measures, to the 
extent possible, and one center will be designated as the central lab to be used for final 
interpretation of PET data. 
Anti-tumor activity will be assessed through radiological tumor assessments conducted at 
baseline, during treatment as specified in the Schedule of Activity, whenever disease 
progression is suspected (eg, symptomatic deterioration), and at the time of withdrawal from 
treatment (if not done in the previous 6 weeks or previous 12 weeks if beyond 18 months in 
Phase 1 and 30 months in Phase 2). 
Assessment of response will be made using RECIST version 1.1 and the modified RECIST 
for intracranial response assessment (Appendix 3).32 Confirmation of response will be 
required at least 4 weeks after initial response is observed. 
All patients’ files and radiologic images must be available for source verification and for 
potential peer/independent central radiology review as determined by the sponsor. 
Instructions for submission of these images will be provided in the Study Reference Manual. 
Upon approval of Amendment 8, tumor assessments will be performed as per local clinical 
practice (see Table 1), tumor assessment information should be retained in the patient’s file 
for documentation purposes. 

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7.5. Banked Biospecimens 
7.5.1. Markers of Drug Response 
Variation in genetic markers and other biomarkers may help to explain some of the 
variability in response seen with some drugs among different individuals. This is referred to 
as pharmacogenomic/biomarker research. Comparing the DNA, RNA, protein, and 
metabolite variation patterns of patients who respond well and those who respond poorly to 
treatment may help to better define the most appropriate group of patients in which to target a 
given treatment. Collecting biospecimens for exploratory pharmacogenomic/biomarker 
analyses and retaining them in the Pfizer BioBank makes it possible to better understand the 
drug’s mechanism of action and to seek explanations for differences in, for example, 
exposure, efficacy, tolerability, or safety not anticipated prior to the beginning of the study. 
Providing these biospecimens is a required study activity for study sites and patients, unless 
prohibited as such by local regulations or ethics committee decision. 
To protect patients’ confidentiality, the banked biospecimens and data generated from them 
will be coded with the patient’s study ID number. Samples will be kept in a facility 
accessible only by badge-swipe. Data will be stored on password-protected computer 
systems. The key between the code and the patient’s personal identifiers will be held at the 
study site; the researchers using the biospecimens and data generated from them will not 
have access to the key nor any personally identifying information. Biospecimens will only 
be used for the purposes described here and in the informed consent document/patient 
information sheet; any other uses require additional ethical approval. Unless a time 
limitation is required by local regulations or ethical requirements, biospecimens will be 
stored indefinitely to allow for future research on the topics described here, including 
research conducted during the lengthy drug development process and also post-marketing 
research. Patients can withdraw their consent for the use of their biospecimens at any time 
by making a request to the investigator, in which case any remaining biospecimen will be 
destroyed; data already generated from the biospecimens will continue to be stored to protect 
the integrity of existing analyses. It is very unlikely that results generated from the 
biospecimens will have any clinical, diagnostic, or therapeutic implications for the individual 
study participants. Patients are notified in the informed consent document/patient 
information sheet that their results will not be given to them, unless required by local laws or 
regulations, in which case results will be returned via the investigator. Results will not be 
provided to family members or other physicians; nor will they be recorded in the patient’s 
medical record. There is no intention to contact patients after completion of the clinical trial. 
A 4 mL blood biospecimen Prep D1 (K2 EDTA whole blood collection optimized for DNA 
analysis) will be collected at the screening visit to be retained for potential 
pharmacogenomic/biomarker analyses related to drug response, unless prohibited by local 
regulations or ethics committee decision. For example, putative safety biomarkers, drug 
metabolizing enzyme genes, drug transport protein genes, or genes thought to be related to 
the mechanism of drug action may be examined. 

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The Banked Biospecimens will be collected from all patients unless prohibited by local 
regulations or ethics committee decision. Detailed collection, processing, storage and 
shipment instructions are provided in the central laboratory manual. 
It is possible that the use of these biospecimens may result in commercially viable products. 
Patients will be advised in the informed consent document/patient information sheet that they 
will not be compensated in this event. 
7.5.2. Additional Research 
Unless prohibited by local regulations, patients will be asked to indicate on the consent form 
whether they will allow the Banked Biospecimens to also be used for the following research: 
• Investigations of the disease under study in the clinical trial, and related conditions; 
• Biospecimens may be used as controls. This includes use in case-control studies of 
diseases for which Pfizer is researching drug therapies; use in characterizing the 
natural variation amongst people in genes, RNA, proteins, and metabolites; and use in 
developing new technologies related to pharmacogenomics/biomarkers. 
Patients need not provide additional biospecimens for the uses described in this section; the 
biospecimens specified in Markers of Drug Response Section will be used. Patients may still 
participate in the clinical trial if they elect not to allow their Banked Biospecimens to be used 
for the additional purposes described in this section. 
7.6. Patient-Reported Outcome Assessments 
7.6.1. EORTC QLQ-C30 and QLQ-LC13 
Patients must complete all EORTC QLQ C30 and QLQ-LC13 self-assessment questionnaires 
in the clinic at the specified time points. At Day -7 (lead- in period) site staff (eg, site 
coordinators) should instruct patients that the assessment should be completed without help 
from friends or family members and also recommend that this assessment be completed in 
the morning. The EORTC questionnaires do not have to be completed if the patient is blind, 
illiterate or if there is no appropriate translation is available at a site for a given patient. All 
scheduled assessments of the EORTC QLQ C30 and QLQ LC13 cannot be taken home and 
must be completed in the clinic prior to any other study or medical procedures. 
The EORTC QLQ-C30 (Version 3.0) and its lung cancer module, 
QLQ-LC13 (Appendix 6 and Appendix 7, respectively) were selected for inclusion in the 
study as they are validated disease specific questionnaires and are also the two most 
commonly used patient reported measures in lung cancer clinical studies.33-36 The EORTC 
QLQ-C30 consists of 30 questions which are incorporated into 5 functional domains 
(physical, role, cognitive, emotional, and social domains); a global quality of life (QOL) 
scale; 3 symptom scales (fatigue, pain, nausea and vomiting scales); and 6 single items that 
assess the additional symptoms (dyspnea, appetite loss, sleep disturbance, constipation, and 
diarrhea) and the perceived financial burden of treatment.33,34 The QLQ-LC13 consists of 
one multi-item scale and 9 single items that assess the specific symptoms (dyspnea, cough, 

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hemoptysis, and site specific pain), side effects (sore mouth, dysphagia, neuropathy, and 
alopecia), and pain medication use of lung cancer patients receiving chemotherapy.35 
Both the EORTC QLQ-C30 and the QLQ-LC13 module require about 15 minutes to 
complete and are available in many languages. Patients will be requested to complete these 
questionnaires at baseline, Day 1 of each cycle until progression and at end of treatment. The 
EORTC QLQ-C30 and the QLQ-LC13 module are collected and evaluated in a different 
manner than the observed or volunteered adverse events. Given these differences, no attempt 
will be made to resolve any apparent discrepancies between observed or volunteered adverse 
events and the additional data collected with the patient reported questionnaires. Additional 
data collected with the EORTC QLQ-C30 and the QLQ-LC13 module will be presented in 
separate tables, figures, and data listings, and will be reviewed in the final study report. 
Adverse event incidence rates will not be calculated from these solicited data but rather from 
the information recorded on the Adverse Event pages on the Case Report Form (CRF). 
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 
serious adverse event (SAE) requiring immediate notification to Pfizer or its designated 
representative. For all AEs, sufficient information should be obtained by the investigator to 
determine the causality of the AE. The investigator is required to assess causality. 
Follow-up by the investigator may be required until the event or its sequelae resolve or 
stabilize at a level acceptable to the investigator, and Pfizer concurs with that assessment. 
As part of ongoing safety reviews conducted by the Sponsor, any non-serious adverse event 
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. 
8.2. Reporting Period 
For SAEs, the active reporting period to Pfizer or its designated representative begins from 
the time that the patient provides informed consent, which is obtained prior to the patient’s 
participation in the study, ie, prior to undergoing any study-related procedure and/or 
receiving investigational product, through and including 28 calendar days after the last 
administration of the investigational product. Serious adverse events occurring to a patient 
after the active reporting period has ended should be reported to the Sponsor if the 
investigator becomes aware of them; at a minimum, all serious adverse events that the 
investigator believes have at least a reasonable possibility of being related to investigational 
product are to be reported to the Sponsor. 

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• AEs (serious and non-serious) should be recorded on the CRF from the time the 
patient has taken at least one dose of investigational product through the patient’s last 
visit. 
• If a patient begins a new anti-cancer therapy, the AE reporting period for non-serious 
AEs ends at the time the new treatment is started. Death must be reported if it occurs 
during the SAE reporting period after the last dose of investigational product, 
irrespective of any intervening treatment. 
8.3. Definition of an Adverse Event 
An AE is any untoward medical occurrence in a clinical investigation patient administered a 
product or medical device; the event need not necessarily have a causal relationship with the 
treatment or usage. Examples of AEs include but are not limited to: 
• Abnormal test findings; 
• Clinically significant symptoms and signs; 
• Changes in physical examination findings; 
• Hypersensitivity; 
• Drug abuse; 
• Drug dependency. 
Additionally, they may include the signs or symptoms resulting from: 
• Drug overdose; 
• Drug withdrawal; 
• Drug misuse; 
• Drug interactions; 
• Extravasations; 
• Exposure during pregnancy (EDP); 
• Exposure via breastfeeding; 
• Medication error; 
• Occupational exposure; 

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• Worsening of signs and symptoms of the malignancy under study should be reported 
as AEs in the appropriate section of the CRF. Disease progression assessed by 
measurement of malignant lesions on radiographs or other methods should not be 
reported as AEs. 
8.4. Medication Errors 
Medication errors may result, in this study, from the administration or consumption of the 
wrong product, by the wrong patient, at the wrong time, or at the wrong dosage strength. 
Such medication errors occurring to a study participant are to be captured on the medication 
error case report form (CRF) which is a specific version of the adverse event (AE) page, and 
on the SAE form when appropriate. In the event of medication dosing error, the sponsor 
should be notified immediately. 
Medication errors are reportable irrespective of the presence of an associated AE/SAE, 
including: 
• Medication errors involving patient exposure to the investigational product; 
• Potential medication errors or uses outside of what is foreseen in the protocol that do 
or do not involve the participating patient. 
Whether or not the medication error is accompanied by an AE, as determined by the 
investigator, the medication error is captured on the medication error version of the adverse 
event (AE) page and, if applicable, any associated adverse event(s) are captured on an 
adverse event (AE) CRF page. 
8.5. Abnormal Test Findings 
The criteria for determining whether an abnormal objective test finding should be reported as 
an AE are as follows: 
• Test result is associated with accompanying symptoms; and/or 
• Test result requires additional diagnostic testing or medical/surgical intervention; 
and/or 
• Test result leads to a change in study dosing outside of protocol-stipulated dose 
adjustments or discontinuation from the study, significant additional concomitant 
drug treatment, or other therapy; and/or 
• Test result is considered to be an AE by the investigator or Sponsor. 
Merely repeating an abnormal test, in the absence of any of the above conditions, does not 
constitute an AE. Any abnormal test result that is determined to be an error does not require 
reporting as an AE. 

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8.6. Serious Adverse Events 
An SAE is any untoward medical occurrence at any dose that: 
• Results in death; 
• Is life-threatening (immediate risk of death); 
• Requires inpatient hospitalization or prolongation of existing hospitalization; 
• Results in persistent or significant disability/incapacity (substantial disruption of the 
ability to conduct normal life functions); 
• Results in congenital anomaly/birth defect; 
• Progression of the malignancy under study (including signs and symptoms of 
progression) should not be reported as an SAE unless the outcome is fatal within the 
safety reporting period. Hospitalization due to signs and symptoms of disease 
progression should not be reported as an SAE. If the malignancy has a fatal outcome 
during the study or within the safety reporting period, then the event leading to death 
must be recorded as an AE and as an SAE with CTCAE Grade 5 (see the Section on 
Severity Assessment). 
Medical and scientific judgment is exercised in determining whether an event is an important 
medical event. An important medical event may not be immediately life-threatening and/or 
result in death or hospitalization. However, if it is determined that the event may jeopardize 
the patient or may require intervention to prevent one of the other AE outcomes, the 
important medical event should be reported as serious. 
Examples of such events are intensive treatment in an emergency room or at home for 
allergic bronchospasm; blood dyscrasias or convulsions that do not result in hospitalization; 
or development of drug dependency or drug abuse. 
8.6.1. Protocol-Specified Serious Adverse Events 
There are no protocol-specified SAEs in this study. All SAEs will be reported by the 
investigator as described in previous sections and will be handled as SAEs in the safety 
database (see the section on SAE Reporting Requirements). 
8.6.2. Potential Cases of Drug-Induced Liver Injury 
Abnormal values in aspartate aminotransferase (AST) and/or alanine aminotransfse (ALT) 
levels concurrent with abnormal elevations in total bilirubin level that meet the criteria 
outlined below in the absence of other causes of liver injury are considered potential cases of 
drug-induced liver injury (potential Hy’s Law cases) and should always be considered 
important medical events. 

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The threshold of laboratory abnormalities for a potential case of drug-induced liver injury 
depends on the patient’s individual baseline values and underlying conditions. Patients who 
present with the following laboratory abnormalities should be evaluated further to 
definitively determine the etiology of the abnormal laboratory values: 
• Patients with AST or ALT and total bilirubin baseline values within the normal range 
who subsequently present with AST or ALT values 3 times the upper limit of 
normal (X ULN) concurrent with a total bilirubin value 2 X UNL 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 upper 
limit of normal, the following threshold values should be used in the definition 
mentioned above: 
• For patients with pre-existing AST or ALT baseline values above the normal 
range, AST or ALT 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 one time 
the upper limit of normal or if the value reaches 3 times the upper limit of 
normal (whichever is smaller). 
The patient should return to the investigational site and be evaluated as soon as possible, 
preferably within 48 hours from awareness of the abnormal results. This evaluation should 
include laboratory tests, detailed history and physical assessment. The possibility of hepatic 
neoplasia (primary or secondary) should be considered. In addition to repeating 
measurements of AST and ALT, laboratory tests should include albumin, creatine kinase, 
total bilirubin, direct and indirect bilirubin, gamma-glutamyl transferase, prothrombin time 
(PT)/international normalized ratio (INR), and alkaline phosphatase. A detailed history, 
including relevant information, such as review of ethanol, acetaminophen, recreational drug 
and supplement consumption, family history, occupational exposure, sexual history, travel 
history, history of contact with a jaundiced person, surgery, blood transfusion, history of liver 
or allergic disease, and work exposure, should be collected. Further testing for acute 
hepatitis A, B, or C infection and liver imaging (eg, biliary tract) may be warranted. All 
cases confirmed on repeat testing as meeting the laboratory criteria defined above, with no 
other cause for liver function test (LFT) abnormalities identified at the time should be 
considered potential Hy’s Law cases irrespective of availability of all the results of the 
investigations performed to determine etiology of the abnormal LFTs. Such potential Hy’s 
Law cases should be reported as SAEs. 

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8.7. Hospitalization 
Hospitalization is defined as any initial admission (even less than 24 hours) in a hospital or 
equivalent healthcare facility or any prolongation of an existing admission. Admission also 
includes transfer within the hospital to an acute/intensive care unit (eg, from the psychiatric 
wing to a medical floor, medical floor to a coronary care unit, or neurological floor to a 
tuberculosis unit). An emergency room visit does not necessarily constitute 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 
work-up of persistent pre-treatment lab abnormality); 
• Social admission (eg, patient has no place to sleep); 
• Administrative admission (eg, for yearly physical examination); 
• Protocol-specified admission during a study (eg, for a procedure required by the study 
protocol); 
• Optional admission not associated with a precipitating clinical AE (eg, for elective 
cosmetic surgery); 
• Hospitalization for observation without a medical AE; 
• Pre-planned treatments or surgical procedures. These should be noted in the baseline 
documentation for the entire protocol and/or for the individual patient; 
• Admission exclusively for the administration of blood products. 

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Diagnostic and therapeutic non-invasive and invasive procedures, such as surgery, should not 
be reported as AEs. However, the medical condition for which the procedure was performed 
should be reported if it meets the definition of an AE. For example, an acute appendicitis 
that begins during the AE reporting period should be reported as the AE, and the resulting 
appendectomy should be recorded as treatment of the AE. 
8.8. Severity Assessment 
The investigator will use the following definitions of Severity in accordance with CTCAE 
v4.03 to describe the maximum intensity of the adverse event. If the event is serious, the 
CTCAE grade reported in the adverse event CRF must be consistent with the description of 
CTCAE grade included in the narrative section of the serious adverse event report. 
 
GRADE Clinical Description of Severity 
0 
No Change from Normal or Reference Range (This grade is not included in the 
Version 4.03 CTCAE document but may be used in certain circumstances.) 
1 
MILD Adverse Event 
2 
MODERATE Adverse Event 
3 
SEVERE Adverse Event 
4 
LIFE-THREATENING consequences; urgent intervention indicated 
5 
DEATH RELATED TO Adverse Event 
Note the distinction between the severity and the seriousness of an AE. A severe event is not 
necessarily an SAE. For example headache may be severe (interferes significantly with the 
patient’s usual function) but would not be classified as serious unless it met one of the 
criteria for SAEs listed above. 
8.9. Causality Assessment 
The investigator’s assessment of causality must be provided for all AEs (serious and 
non-serious); the investigator must record the causal relationship in the CRF, as appropriate, 
and report such an assessment in accordance with the serious adverse reporting requirements 
if applicable. An investigator’s causality assessment is the determination of whether there 
exists a reasonable possibility that the investigational product caused or contributed to an 
AE; generally the facts (evidence) or arguments to suggest a causal relationship should be 
provided. If the investigator does not know whether or not the investigational product caused 
the event, then the event will be handled as “related to investigational product” for reporting 
purposes, as defined by the Sponsor (see the Section on Reporting Requirements). If the 
investigator's causality assessment is “unknown but not related to investigational product”, 
this should be clearly documented on study records. 

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In addition, if the investigator determines that an SAE is associated with study procedures, 
the investigator must record this causal relationship in the source documents and CRF, as 
appropriate, and report such an assessment in accordance with the SAE reporting 
requirements, if applicable. 
8.10. Exposure During Pregnancy 
For both unapproved/unlicensed products and for marketed products, an exposure during 
pregnancy occurs if: 
1. A female becomes, or is found to be, pregnant either while receiving or having been 
exposed (eg, because of treatment or environmental exposure) to the investigational 
product; or the female becomes, or is found to be pregnant after discontinuing and/or 
being exposed to the investigational product; 
An example of environmental exposure would be a case involving direct contact with 
a Pfizer product in a pregnant women (eg, a nurse reports that she is pregnant and has 
been exposed to chemotherapeutic products). 
2. A male has been exposed (eg, because of treatment or environmental exposure) to the 
investigational product prior to or around the time of conception and/or is exposed 
during his partner’s pregnancy. 
If a study patient or study patient’s partner becomes or is found to be pregnant during the 
study patient’s treatment with the investigational product, the investigator must submit this 
information to the Pfizer Drug Safety Unit on a Serious Adverse Event Report Form and 
Exposure in Utero (EIU) Supplemental Form regardless of whether an SAE has occurred. In 
addition, the investigator must submit information regarding environmental exposure to a 
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 EIU Form. This must be 
done irrespective of whether an AE has occurred and within 24 hours of awareness of the 
exposure. The information submitted should include the anticipated date of delivery (see 
below for information related to termination of pregnancy). 
Follow-up is conducted to obtain general information on the pregnancy and its outcome for 
all EIU reports with an unknown outcome. The investigator will follow the pregnancy until 
completion (or until pregnancy termination) and notify Pfizer of the outcome as a follow up 
to the initial EIU Form. In the case of a live birth, the structural integrity of the neonate can 
be assessed at the time of birth. In the event of a termination, the reason(s) for the 
termination should be specified and, if clinically possible, the structural integrity of the 
terminated fetus should be assessed by gross visual inspection (unless pre-procedure test 
findings are conclusive for a congenital anomaly and the findings are reported). 
If the outcome of the pregnancy meets the criteria for an SAE (ie, ectopic pregnancy, 
spontaneous abortion, intrauterine fetal demise, neonatal death, or congenital anomaly [in a 
live born baby, a terminated fetus, an intrauterine fetal demise or a neonatal death]), the 
investigator should follow the procedures for reporting SAEs. 

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Additional information about pregnancy outcomes that are reported as SAEs follows: 
• Spontaneous abortion includes miscarriage and missed abortion; 
• Neonatal deaths that occur within 1 month of birth should be reported, without regard 
to causality, as SAEs. In addition, infant deaths after 1 month should be reported as 
SAEs when the investigator assesses the infant death as related or possibly related to 
exposure to the investigational product. 
Additional information regarding the exposure during pregnancy may be requested by the 
investigator. Further follow-up of birth outcomes will be handled on a case-by-case basis 
(eg, follow-up on preterm infants to identify developmental delays). In the case of paternal 
exposure, the investigator will provide the study patient with the Pregnant Partner Release of 
Information Form to deliver to his partner. The Investigator must document in the source 
documents that the patient was given the Pregnant Partner Release of Information Form to 
provide to his partner. 
8.11. Occupational Exposure 
An occupational exposure occurs when during the performance of job duties, a person 
(whether a healthcare professional or otherwise) gets in unplanned direct contact with the 
product, which may or may not lead to the occurrence of an adverse event. 
An occupational exposure is reported to the drug safety unit within 24 hours of the 
investigator’s awareness, using the SAE Report form, regardless of whether there is an 
associated AE/SAE. Since the information does not pertain to a patient enrolled in the study, 
the information is not reported on a CRF, however a copy of the completed SAE Report form 
is maintained in the investigator site file. 
8.12. Withdrawal Due to Adverse Events (Also See Section on Patient Withdrawal) 
At least 28 days, and no more than 35 days after discontinuation of treatment patients will 
return to undergo assessment for resolution of any treatment-related toxicity. Patients 
continuing to experience toxicity at this point following discontinuation of treatment will 
continue to be followed at least every 4 weeks until resolution or determination, in the 
clinical judgment of the Investigator, that no further improvement is expected. Patients 
discontinuing treatment for progression of disease or for reasons other than progression of 
disease will enter the follow-up phase. The survival follow-up will be performed every 
2 months and will include also the collection of information on subsequent anticancer 
therapies (telephone contact is acceptable). 
Withdrawal due to AEs should be distinguished from withdrawal due to other causes, 
according to the definition of AE noted earlier, and recorded on the appropriate AE CRF 
page. 
When a patient withdraws because of an SAE, the SAE must be reported in accordance with 
the reporting requirements defined below. 

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8.13. Eliciting Adverse Event Information 
The investigator is to report all directly observed AEs and all AEs spontaneously reported by 
the study patient. In addition, each study patient will be questioned about AEs. 
8.14. Reporting Requirements 
Each AE is to be assessed to determine if it meets the criteria for SAEs. If an SAE occurs, 
expedited reporting will follow local and international regulations, as appropriate. 
8.14.1. Serious Adverse Event Reporting Requirements 
If an SAE occurs, Pfizer is to be notified within 24 hours of investigator awareness of the 
event. 
In particular, if the SAE is fatal or life-threatening, notification to Pfizer must be made 
immediately, irrespective of the extent of available AE information. This timeframe also 
applies to additional new information (follow-up) on previously forwarded SAE reports as 
well as to the initial and follow-up reporting of exposure during pregnancy, exposure via 
breastfeeding and occupational exposure cases. 
In the rare event that the investigator does not become aware of the occurrence of an SAE 
immediately (eg, if an outpatient study patient initially seeks treatment elsewhere), the 
investigator is to report the event within 24 hours after learning of it and document the time 
of his/her first awareness of the AE. 
For all SAEs, the investigator is obligated to pursue and provide information to Pfizer in 
accordance with the timeframes for reporting specified above. In addition, an investigator 
may be requested by Pfizer to obtain specific additional follow-up information in an 
expedited fashion. This information collected for SAEs is more detailed than that captured 
on the AE CRF. In general, this will include a description of the AE in sufficient detail to 
allow for a complete medical assessment of the case and independent determination of 
possible causality. Information on other possible causes of the event, such as concomitant 
medications, vaccines and/or illnesses must be provided. In the case of a patient death, a 
summary of available autopsy findings must be submitted as soon as possible to Pfizer or its 
designated representative. 
8.14.2. Non-Serious Adverse Event Reporting Requirements 
All AEs will be reported on the AE page(s) of the CRF. It should be noted that the form for 
collection of SAE information is not the same as the AE CRF. Where the same data are 
collected, the forms must be completed in a consistent manner. For example, the same AE 
term should be used on both forms. AEs should be reported using concise medical 
terminology on the CRFs as well as on the form for collection of SAE information. 
8.14.3. Sponsor’s Reporting Requirements to Regulatory Authorities 
Adverse event 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 trial 
will be documented in a Statistical Analysis Plan (SAP), which will be maintained by Pfizer. 
This document may modify the plans outlined in the protocol; however, any major 
modifications of the primary endpoint and/or its analysis will also be reflected in a protocol 
amendment. 
9.1. Analysis Sets 
• Full analysis set. 
The full analysis set includes all enrolled patients, regardless of whether or not treatment 
was received. 
• Intention-To-Treat (ITT) analysis set. 
The ITT analysis set includes all enrolled patients with an ALK or ROS1 rearrangement 
as per local test and who received at least one dose of study medication (including 
Day – 7 dose). 
• Per protocol analysis sets. 
Patients with CNS metastases based on Investigator Assessment 
• Subset of the ITT analysis set including only patients with CNS metastases at 
study entry (ie, with Lesions having Disease Site=Brain) according to Investigator 
Assessment 
• Patients with CNS metastases based on Independent Central Review 
• Subset of the ITT analysis set including only patients with CNS metastases at 
study entry (ie, with Lesions having Disease Site=Brain) according to 
Independent Central Review 
• Evaluable for MTD (Phase 1 only): all enrolled patients who receive at least 
75% of the planned PF-06463922 doses in the first cycle. Patients who receive 
less than 75% of the planned PF-06463922 doses in the first cycle due to DLT are 
also considered evaluable for MTD. 
• Safety analysis set. 
The safety analysis set includes all enrolled patients who receive at least one dose of 
study medication (including Lead-in dose). 

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• PK analysis set: 
The PK parameter analysis set is defined as all enrolled patients who receive at least one 
dose of PF-06463922 (including Day -7 dose) and have sufficient information to estimate 
at least 1 of the PK parameters of interest (Cmax or AUC) for PF-06463922. 
All other analysis sets will be documented in the SAP. 
9.2. Statistical Methods and Properties 
9.2.1. Methods 
The Phase 1 portion of this study employs a modified CRM to estimate the MTD. The 
modified CRM algorithm utilizes the Bayesian methodology to continuously learn about the 
dose-toxicity relationship after each cohort’s DLT data becomes available. The underlying 
model assumption is that DLT rate at each dose can be expressed as Pr (DLT|dose x)=f(x, ), 
where f is a monotonically increasing function in dose x and  is an unknown parameter with 
prior distribution placed on it at the beginning of the trial. The first 2 cohorts patients will be 
assigned to 10 mg/QD and 25 mg/QD respectively if the DLT data warrants dose escalation. 
After the DLT data of the 25 mg/QD cohort becomes available (~3 wks), the prior 
distribution of  is updated based on their DLT responses and becomes a posterior 
distribution. The current estimate of MTD is calculated as MTD=f-1 (0.33, ), given 
posterior information about  (ie, DLT data + modeling), and the next cohort’s dose 
assignment is chosen as the dose closest to this estimated MTD but not exceeding it. This 
process is continued until 1 of the stopping rules below is triggered. 
1. Maximum sample size of 36 patients has been reached. 
2. MTD has been identified with sufficient accuracy: twelve (12) patients have been 
accumulated on a dose that is currently estimated to be the MTD likely to be the 
RP2D, and there are at least 12 patients overall enrolled in the trial. 
3. All doses appear to be overly toxic and the MTD can not be determined in the current 
trial setting. 
Starting from the third cohort and until the end of trial, the above described modified CRM 
algorithm constantly incorporates additional information about dose-DLT relationship 
learned from the data via modeling and that is reflected on the projected MTD. By design, 
such dose allocation procedure will eventually cluster dose assignments around the dose 
yielding a DLT rate closest to but no more than 33%. Additional patients may be enrolled to 
further explore doses below the MTD based on the totality of the safety data. 
Once one of the aforementioned conditions for stopping the CRM is met, the dose identified 
as MTD will be evaluated together with information gathered from PK analyses and the 
overall safety profile in order to determine the RP2D. The dose(s) likely to be considered the 
RP2D will be expanded to 12 patients if not already tested within the CRM context in order 
to confirm the RP2D. Due to the variability of binary data in small samples, DLTs may be 
observed in a first cohort(s) assigned 10 mg simply by chance even when the true PR 

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(DLT|10 mg) is fairly low. This would result in the estimated posterior DLT rate at 10 mg 
(and all higher doses) to exceed the targeted 33% very early in the trial, triggering a futility 
stop when very few patients have been treated. To prevent stopping the trial prematurely for 
futility in such cases, a step-down option with a dose of 5 mg is added to the dose grid. This 
dose will be explored only if a high DLT rate (2/3) occurs in the first cohort assigned to 
10 mg, ie, it will not be used as a starting dose and the algorithm will always assign the first 
cohort of patients to 10 mg. 
9.2.2. Simulations for CRM Design in Phase 1 
Several simulations were performed to fine-tune the CRM performance and to study 
operating characteristics of the chosen “best” CRM design. Below is a brief description of 
the simulation setup and key findings. 
Different combinations of stopping rules (6, 9, and 12 patients on MTD) and maximum 
sample size were examined. Competing designs were evaluated against 6 different plausible 
scenarios of dose-toxicity profile varying in steepness of dose-DLT curve and location of the 
true MTD within the studied dose range. These scenarios are summarized in Table 17 below. 
Table 17. Probability of DLT as a Function of Dose 
 
Dose-Toxicity Curve Scenario 
Dose 
Sc. 1: 
MTD= 
25-flat 
Sc. 4: 
MTD= 
25-steep 
Sc. 2: 
MTD= 
100-flat 
Sc. 5: 
MTD= 
100-steep 
Sc. 3: 
MTD= 
400-flat 
Sc. 6: 
MTD= 
400-steep 
10 mg/QD 
0.3 
0.1 
0.05 
0.01 
0.01 
0.00 
25 mg/QD 
0.333 
0.3333 
0.1 
0.02 
0.02 
0.00 
50 mg/QD 
0.4 
0.6 
0.175 
0.05 
0.03 
0.00 
75 mg/QD 
0.45 
0.85 
0.25 
0.15 
0.04 
0.00 
100 mg/QD 
0.5 
0.95 
0.333 
0.333 
0.05 
0.00 
150 mg/QD 
0.6 
1 
0.5 
0.7 
0.08 
0.00 
200 mg/QD 
0.7 
1 
0.65 
0.9 
0.12 
0.00 
300 mg/QD 
0.8 
1 
0.85 
1 
0.22 
0.10 
400 mg/QD 
0.9 
1 
1 
1 
0.333 
0.333 
 
For each of the competing designs (ie, CRM design variant), the following operating 
characteristics were assessed, by scenario, to further quantify the trade-off between precision 
of MTD estimation and design cost: 
• Probability to select MTD. 
• Design cost: 
• Average Sample Size; 
• Average Number of DLTs; 
• Average Proportion of DLTs. 

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These operating characteristics are summarized in Table 18 below for the final design 
selected based on 1000 trials simulated. The magnitude of trade-off between quality of MTD 
information obtained and design costs (such as sample size, and observed toxicities) varies 
depending on the underlying dose-toxicity relationship. A specific variant of CRM design 
(stopping rule with 12 patients on MTD) was chosen among multiple variants examined 
(6, 9, or 12 patients on MTD) as the most optimal in terms of MTD precision/design cost 
trade-off. 
Table 18. Operating Characteristics of the CRM in Phase 1 
 
MTD Dose Selection Decision (Probability) 
Scenario 
10 mg/ 
QD 
25 mg/ 
QD 
50 mg/ 
QD 
75 mg/ 
QD 
100 mg/ 
QD 
150 mg/ 
QD 
200 mg/ 
QD 
300 mg/ 
QD 
400 mg/ 
QD 
Averag 
e size 
Average 
Num 
DLTs 
Average 
DLTs (%) 
MTD 
25 flat 
0.142 0.107 0.091 0.043 0.009 0.001 
0 
0 
0 
12.9 
4.6 
0.4 
MTD 
25 steep 
0.3 
0.426 0.025 
0 
0 
0 
0 
0 
0 
19.5 
6.2 
0.3 
MTD 
100 flat 
0.003 0.017 
0.15 
0.305 0.356 0.089 0.004 
0 
0 
26.6 
7.2 
0.3 
MTD 
100 steep 
0 
0 
0.008 0.258 0.702 0.015 
0 
0 
0 
27.7 
7.6 
0.3 
MTD 
400 flat 
0 
0 
0 
0 
0.001 
0.02 
0.138 0.497 0.327 
27.9 
4.2 
0.2 
MTD 
400 steep 
0 
0 
0 
0 
0 
0 
0 
0.299 0.701 
28.2 
4.1 
0.1 
 
9.3. Sample Size Determination 
Phase 1 
Similar to the conventional 3+3 design, the exact sample size of the CRM design in the 
Phase 1 cannot be prespecified because of the dynamic feature of the design. The minimum 
and maximum sample sizes after which the Phase 1 can be stopped and MTD declared are 
12 and 36 patients, respectively. The actual sample size of the Phase 1 will lie somewhere 
between 12 and 36 depending on the underlying dose-toxicity profile and variability in actual 
data realization. 
Typically, at least 3 patients will be treated at each dose level tested. 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 from 0 to 12. At least 12 patients will be treated at the 
dose likely to be considered the RP2D. 
Phase 2 
For subpopulations EXP1-EXP-5 described in Section 3.1 the goal of the primary analysis of 
objective response will be to estimate the Objective Response Rates (ORR) and their 
95% exact confidence intervals (Clopper-Pearson). 
For EXP-1 the target sample size is 30 patients. 

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EXP-2 and EXP-3A+EXP-3B were considered similar; the subgroups were to be analyzed 
separately and also as a pooled set EXP-2:3A:3B for a combined efficacy analysis. As the 
population of patients receiving only crizotinib (EXP-2) was limited, a possible lower 
enrollment in this group was to be compensated with patients enrolled in EXP-3, 
targeting 80 patients in total between EXP-2 and EXP-3A+EXP3B combined. 
For EXP-4, the target sample size is increased to 70 patients, allowing more precise 
estimation in this group with diverse prior treatments. 
For EXP-5 the target sample size remains unchanged at 40 patients. 
As EXP-4 and EXP-5 represent the more advanced line of treatment of patients treated in 
3rd -4th line, a pooled analysis of efficacy will be conducted on the resulting target sample 
size of 110 patients treated with PF-06463922 after at least two prior ALK TKI. 
Table 19 below shows possible estimated ORR and 95% CIs for different level of responses 
in populations of 30, 40 patients, 70 and 80 patients. 
Table 19.  Estimated ORRs and Related 95% Confidence Intervals 
 
Responses/Cohort Sample 
Size 
ORR (Estimated 95% CI) 
21/30 
70% (50.6-85.3) 
23/30 
77% (57.7-0.90) 
25/30 
83% (65.3-94.4) 
16/40 
40% (24.9-56.7) 
20/40 
50% (33.8-66.2) 
24/40 
60% (43.3-75.1) 
24/70 
34% (23.3-46.6) 
28/70 
40% (28.5-52.4) 
32/70 
45% (33.7-58.1) 
32/80 
40% (29.2-51.6) 
40/80 
50% (38.6-61.4) 
48/80 
60% (48.4-70.8) 
 
For subpopulation EXP-6 described in Section 3.1, the group-sequential two-stage design 
using an O’Brien-Fleming40 non-binding stopping boundary for futility to test the null 
hypothesis that the response rate P ≤0.30 versus the alternative that P ≥0.50 has an expected 
sample size of 31 and a probability of early termination of 0.40 under the null 
hypothesis. This is based on a target 1-sided type I error rate of 0.10 and power of 
0.90. After testing the drug on 20 patients in the first stage, the trial will be terminated if 
≤5 patients respond. If the trial proceeds to the second stage, a total of 39 patients will be 
studied. If the total number of responding patients is ≥16 for this subpopulation, then the null 
hypothesis will be rejected. 

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9.4. Efficacy Analysis 
9.4.1. Primary Analysis 
Phase 1 
In Phase 1, anti-tumor activity is a secondary objective. 
Phase 2 
The following analyses of response will be performed according to independent central 
radiology assessment and derived investigator assessment, respectively. The analyses based 
on the independent central radiology assessment will be considered primary. 
Objective Response Rate (ORR) 
ORR is defined as the percent of patients with Best Overall Response as confirmed Complete 
Response (CR) or confirmed Partial Response (PR) according to RECIST version 1.1 relative 
to the ITT analysis set. ORR will be calculated for subgroups EXP-1:6 and will be provided 
along with the corresponding 95% exactconfidence intervals. 
Waterfall plots displaying the best % change from baseline in tumor size and spider plots 
displaying the % change in tumor size from baseline across visits will also be presented. 
Intracranial ORR (IC-ORR) 
Intracranial ORR is defined as the percent of patients with intracranial response (ie, Best 
Overall Intracranial Response as confirmed Complete Response (CR) or confirmed Partial 
Response (PR) considering only the Lesions having Disease Site=Brain) relative to patients 
with CNS metastases analysis sets. ORR will be calculated for subgroups EXP-1:6 and will 
be provided along with the corresponding 95% exact confidence interval. 
Waterfall plots displaying the best % change from baseline in tumor size of intracranial 
lesions and a spider plots displaying the % change in tumor size of intracranial lesions from 
baseline across visits will also be presented. 
For patients treated in EXP-3, ORR and IC-ORR will also be presented separately for 
subgroups EXP-3A and EXP-3B. 
Different Pooled ORRs/IC-ORR will be calculated on the groups resulting from pooling ITT 
analysis set of the following subpopulations: 
- EXP-2:5 (for PF-06463922 treatment after at least one prior ALK TKI). 
- EXP-2:3A (for PF-06463922 treatment after prior crizotinib). 
- EXP-3B (for PF-06463922 treatment after one prior ALK TKI different from crizotinib). 
- EXP-3B:5 (for PF-06463922 treatment after at least one prior 2nd generation ALK TKI). 
- EXP-4:5 (for PF-06463922 treatment after at least two prior ALK TKIs). 

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A waterfall plot displaying the best percentage change in tumor size will also be provided for 
each pooled analysis set. 
9.4.2. Analysis of Secondary Endpoints 
Phase 1 
For the Phase 1 all the analyses of efficacy endpoints but OS will be made according to both 
independent central radiology assessment and derived investigator assessment, respectively, 
and endpoints will be calculated pooling the populations from all of the dose escalation 
cohorts. 
ORR 
ORR is defined as the percent of patients with Best Overall Response as confirmed CR or PR 
according to RECIST version 1.1 relative to the ITT analysis set and will be provided along 
with the corresponding 95% exact confidence interval. 
For Phase 1 only, in addition to the ORR based on confirmed responses a second ORR 
including Unconfirmed CR and Unconfirmed PR will also be calculated. 
A waterfall plot displaying the best % change from baseline in tumor size and a spider plot 
displaying the % change in tumor size from baseline across visits will also be presented. 
Intracranial ORR 
Intracranial ORR is defined as the percent of patients with intracranial response (ie, Best 
Overall Intracranial Response as confirmed Complete Response (CR) or confirmed Partial 
Response (PR) considering only the Lesions having Disease Site=Brain) relative to patients 
with CNS metastases analysis set, and will be provided along with the corresponding 
95% exact confidence interval. 
A waterfall plot displaying the best % change from baseline in tumor size of intracranial 
lesions and a spider plot displaying the % change in tumor size of intracranial lesions from 
baseline across visits will also be presented. 
Phase 1 and Phase 2 
In Phase 2, estimates of efficacy endpoints will be calculated separately for subgroups 
EXP-1:6; and for patients treated in EXP-3 also separately for subgroups EXP-3A and 
EXP-3B. 
In addition, pooled estimates will be calculated on the groups resulting from pooling ITT 
analysis set of the following subpopulations: 
- EXP-2:5 (for PF-06463922 treatment after at least one prior ALK TKI). 
- EXP-2:3A (for PF-06463922 treatment after prior crizotinib). 
- EXP-3B (for PF-06463922 treatment after one prior ALK TKI different from crizotinib). 

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- EXP-3B:5 (for PF-06463922 treatment after at least one prior 2nd generation ALK TKI). 
- EXP-4:5 (for PF-06463922 treatment after at more than one prior ALK TKI). 
Disease Control Rate (DCR) at 12 and 24 Weeks 
DCR at 12 and 24 weeks is defined as the percent of patients with Disease Control at 12 and 
24 weeks (ie, having at week 12/24 or later a status of response [CR or PR] or of Stable 
Disease [SD]) relative to the patients in the ITT analysis set and will be provided along with 
the corresponding 95% exact confidence interval. 
Time-to-Event Endpoints 
PFS is defined as the time from first dose to first documentation of objective disease 
progression or to death on study due to any cause, whichever comes first. 
OS is defined as the time from randomization to the date of death due to any cause. For 
patients still alive at the time of analysis, the OS time will be censored on the last date the 
patients were known to be alive. 
Censoring criteria will be described in details in the SAP. 
Estimates of the time-to-event curves using the Kaplan-Meier method will be presented. 
This method will be applied to derive the median event time and a confidence interval for the 
median as well as the 1-year and 18-month survival probabilities with related confidence 
intervals. The confidence intervals will be 2-sided, have a stated coverage probability of 
95%, and be calculated using normal approximation methods. 
Duration of Response 
DR is defined as the time from the first documentation of objective tumor response (CR or 
PR) to the first documentation of disease progression or to death due to any cause, whichever 
occurs first. DR will only be calculated for the subgroup of patients with a confirmed 
objective tumor response, will be summarized using the Kaplan-Meier method and displayed 
graphically where appropriate. The median event time (if appropriate) and 2-sided 95% CI 
for the median will be provided. Since the number of patients with a confirmed CR or PR 
may be small, the use of Kaplan-Meier method may be limited and the DR may be 
summarized using descriptive statistics. 
All the analyses will be repeated also for IC-DR (Duration of Intracranial Response) 
considering patients with intracranial response (ie, Best Overall Intracranial Response as 
confirmed Complete Response (CR) or confirmed Partial Response (PR) considering only 
the Lesions having Disease Site=Brain) 

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Time to Tumor Response 
TTR is defined as the time from first dose to first documentation of objective tumor response 
(CR or PR). For patients whose OR proceeds from PR to CR, the onset of PR is taken as the 
onset of response. TTR will only be calculated for the subgroup of patients with a confirmed 
objective tumor response. 
All the analyses will be repeated also for IC-TTR (Time To Intracranial Response) 
considering patients with intracranial response (ie, Best Overall Intracranial Response as 
confirmed Complete Response (CR) or confirmed Partial Response (PR) considering only 
the Lesions having Disease Site=Brain). 
Probability of first event being a CNS progression, non CNS progression, or death. 
The probability of first event being a CNS progression, non CNS progression, or death will 
be estimated by using cumulative incidence functions relative to the analysis 
populations/subgroups based on both independent central review and investigator 
assessments. 
All the analyses will be repeated also on patients with brain lesions at study entry in the 
analysis populations/subgroups as specified in Appendix 2 (ie, considering only those having 
at least one Baseline Lesion having Disease Site=Brain). 
Phase 2 Only 
Time To Progression 
TTP is defined as the time from first dose to first documentation of objective disease 
progression. Censoring criteria will be described in the SAP. 
Estimates of the time-to-event curves using the Kaplan-Meier method will be presented. 
This method will be applied to derive the median event time and a confidence interval for the 
median, as well as the 1-year and 18-month survival probabilities with related confidence 
intervals. The confidence intervals will be 2-sided, have a stated coverage probability of 
95%, and be calculated using normal approximation methods. 
9.4.3. Analysis of Exploratory Endpoints 
Phase 1 
For patients in Phase 1 TTP will be analyzed. Estimates of the time-to-event curves from the 
Kaplan-Meier method will be presented. This method will be applied to derive the median 
event time and a confidence interval for the median, as well as the 1-year and 18-month 
survival probabilities with related confidence intervals. The confidence intervals will be 
2- sided, have a stated coverage probability of 95%, and be calculated using normal 
approximation methods. 

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9.5. Analysis of Other Endpoints 
9.5.1. Analysis of Pharmacokinetics 
9.5.1.1. Single- and Multiple-Dose PF-06463922 PK Analysis 
Plasma pharmacokinetic parameters including the maximum plasma concentration (Cmax), 
time to maximum plasma concentration (Tmax), and area under the plasma concentration 
versus time curve (AUClast) for PF-06463922 will be estimated using non-compartmental 
analysis. If data permit or if considered appropriate, area under the plasma concentration 
versus time curve to infinity (AUCinf), terminal elimination half-life (t1/2), oral plasma 
clearance (CL/F), apparent volume of distribution (Vz/F), accumulation ratio (Rac) and 
linearity ratio (Rss) will be also estimated. The single dose and steady-state PK parameters 
will be summarized descriptively by dose, cycle and day. 
For PF-06463922 concentrations, concentrations will be summarized descriptively (n, mean, 
SD, CV, median, minimum, maximum, geometric mean and its associated CV) by dose, 
cycle, day and nominal time. Individual patient and median profiles of the 
concentration-time data will be plotted by dose, cycle and day (single dose and steady-state) 
using nominal times. Median profiles will be presented on both linear-linear and log-linear 
scales. 
Dose normalized AUCinf (AUCτ at steady state), AUClast and Cmax will be plotted against 
dose (using a logarithmic scale) by cycle and day. These plots will include individual patient 
values and the geometric means for each dose. These plots will be used to help understand 
the relationship between the PK parameters and dose. 
The observed accumulation ratio and the linearity ratio will be summarized descriptively. 
Each will be analyzed after natural log transformation using a one-way analysis of variance 
with a single term for dose. The means and 90% confidence intervals (CIs) obtained from 
the model will be back-transformed to provide means and 90% CIs for the accumulation and 
linearity ratios for each dose. 
Trough concentrations will be plotted for each dose using a box-whisker plot by cycle and 
day within cycle in order to assess the attainment of steady-state. 
Urine PK parameters (Ae%, CLr) for PF-06463922 will also be estimated and summarized. 
9.5.1.2. Effect of PF-06463922 on MDZ Pharmacokinetics 
Plasma concentration-time data of MDZ in the absence and presence of PF-06463922 will be 
analyzed using non-compartmental methods to estimate the following PK parameters in 
individual patient: Cmax, Tmax, AUC0-last, and, if data permit, AUC0-∞, t1/2, CL/F and Vd/F. 
Descriptive statistics will be provided for these PK parameters in tabular form. 
The pharmacokinetic parameter AUC0-last, AUC0-∞ (if data permit) and Cmax will be utilized to 
estimate the effect of multiple doses of PF-06463922 on MDZ PK. 

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9.5.1.3. Effect of Food on PF-06463922 Pharmacokinetics 
For the evaluation of the food effect, PF-06463922 plasma concentration-time data will be 
compared on Day -7 to Cycle 1/Day 1. Natural log transformed AUC0-last, AUC0-∞ (if data 
permit) and Cmax values will be analyzed using a mixed effects model with sequence and 
treatment (fed, fast) as fixed effects and patient within sequence as a random effect. 
Estimates of the adjusted mean differences (Fed-Fasted) and corresponding 90% confidence 
intervals will be obtained from the model. The adjusted mean differences and 90% 
confidence intervals for the differences will be exponentiated to provide estimates of the 
ratios of adjusted geometric means (Fed/Fasted) and 90% confidence intervals for the ratios. 
9.5.1.4. Population Pharmacokinetic Analysis or PK/PD Modeling 
Pharmacokinetic and pharmacodynamic data from this study may be analyzed using 
modeling approaches and may also be pooled with data from other studies to investigate any 
association between PF-06463922 exposure and biomarkers or significant safety endpoints. 
The results of these analyses, if performed, may be reported separately. 
9.5.1.5. Metabolite Profiling 
Plasma metabolite profiling will be summarized in a separate report and not included in the 
clinical study report (CSR). 
9.5.1.6. Statistical Analysis of Biomarker Endpoint 
Biomarkers will be assessed separately for blood and tumor biopsy tissue samples. In each 
case, summaries of baseline levels and changes from baseline will be reported. Summary 
statistics may include the mean and standard deviation, median, and minimum/maximum 
levels of biomarker measures or frequency statistics, as appropriate. 
Data from biomarker assays will be analyzed using graphical methods and descriptive 
statistics such as linear regression, t test, and analysis of variance (ANOVA). The statistical 
approach will may examine correlations of biomarker results with pharmacokinetic 
parameters and measures of anti tumor efficacy. 
Due to the exploratory nature of the proposed biomarkers, the data analysis will be conducted 
with the goal of identifying biomarkers with the strongest concordance to clinical outcome, 
encompassing both safety and efficacy. Candidate biomarkers will be validated in 
subsequent trials. 
9.6. Safety Analysis 
Summaries and analyses of the primary safety endpoint for the Phase 1 will be based on the 
per protocol analysis set. Summaries and analyses of safety parameters on 
Phase 1, Phase 2 and the DDI/Holter monitoring study will be based on the Safety Analysis 
Set. 

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9.6.1. Analysis of Primary Endpoint for Phase 1 
• Dose-Limiting Toxicity (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. 
9.6.2. Analysis of Secondary Safety Endpoints for Phase 1, Phase 2, and the DDI/Holter 
monitoring study 
Adverse Events 
Adverse Events (AEs) will be graded by the investigator according to the Common 
Terminology Criteria for Adverse Events (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, 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). 
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. 
Vital Signs 
Changes from baseline in vital signs, including body weight, blood pressure and heart rate 
will be summarized. 
Left Ventricular Ejection Fraction (LVEF) 
For patients with MUGA scans or echocardiograms, individual LVEF proportion (%) and its 
changes from baseline will be summarized by time point. The number of patients and the 
percentage whose maximum decrease from baseline in LVEF is equal or greater than 
20% will be calculated. 
Mini Mental State Examination (Phase 1 only): 
Changes of the the Total Mini Mental State Examination Score will be described across 
cycles. 

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9.6.3. ECG Analysis 
The analysis of ECG results will be based on Safety Population patients with baseline and 
on-treatment ECG data. ECG collected prior to the first day of dosing will be considered the 
baseline ECG. 
ECG measurements (an average of the triplicate measurements) will be used for the 
statistical analysis and all data presentations. Any data obtained from ECGs repeated for 
safety reasons after the nominal time points will not be averaged along with the preceding 
triplicates. Interval measurements from repeated ECGs will be included in the outlier 
analysis as individual values obtained at unscheduled time points. 
QT intervals will be corrected for heart rate (QTc) using standard correction factors (ie, 
Bazett’s, Fridericia’s and possibly a study specific factor). The adequacy of the correction 
method will be assessed graphically (plots of QT and QTc versus RR) and supplementary 
transformations may be considered, as appropriate. Data will be summarized and listed for 
QT, HR, RR, PR, QRS, QTcF, and QTcB by cycle, day and dose. Individual QTc (all 
evaluated corrections) intervals will be listed by time and dose. The most appropriate 
correction factor will be selected and used for the following analyses of central tendency and 
outliers and used for the study conclusions. Descriptive statistics (n, mean, median, standard 
deviation, minimum, and maximum) will be used to summarize the absolute QTc value and 
changes from baseline in QTc after treatment by, cycle, day, dose and by time point. For 
each patient and by treatment, the maximum change from baseline will be calculated as well 
as the maximum post-baseline value across time points. Outlier analysis of the QTc data will 
be conducted and summarized as follows: 
• The number of patients with maximum change from baseline in QTc (<30, 30-60, and 
60 msec); 
• The number of patients with maximum post-dose (post-baseline) QTc (<450, 
450-<480, 480-<500, and >500 msec). 
Shift tables will be provided for baseline vs worst on study QTc (one or more correction 
method will be used) using Maximum CTCAE Grade V4.03. As well as tables of ECG 
abnormality at baseline (yes, no, not done: (n, %)). Patients experiencing clinically-relevant 
morphological ECG changes will be summarized (including frequency and percentage). 
The effect of drug concentrations on QTc change from baseline will be explored graphically. 
Additional concentration-QTc analyses may be performed. Data may be pooled with other 
study results and/or explored further with PK/PD models. 
9.7. Pharmacodynamic Analysis 
CTC-based pharmacodynamic analysis is an exploratory objective. For CTC enumeration, 
summary statistics (eg, the mean and standard deviation, median, and minimum/maximum 
levels of continuous, and frequencies and percentages of categorical biomarker measures) 
will be determined at baseline, end of C2/pre dose on C3D1 and end of study treatment. For 
each pair of specimens, the percent change from baseline of these same parameters might 

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also be calculated. The statistical approach may examine correlations of CTC results with 
pharmacokinetic parameters and measures of anti-tumor efficacy. Per Amendment 4, this 
analysis will no longer be performed and has been removed as a secondary endpoint. 
9.8. Patient Reported Outcomes Analyses 
At each time point, the number and percentage of patients who complete the QLQ-C30 and 
QLQ-LC13 will be summarized in a table, as will the reasons for non-completion of these 
measures. 
Rates of improvement will be evaluated over each cycle in the symptom scales, in the 
functioning scale and in the global QOL scale. In the symptom scales improvement is 
defined as decrease of at least 10 points. In the functioning and global QOL scales 
improvement is defined as an increase of at least 10 points. 
The number and proportion of patients who improved, worsened, or remained stable for all of 
the symptom and functional domains, global QOL, and single items of the EORTC 
QLQ-C30 and the QLQ-LC-13 will be summarized by dosing cohort/subgroup. Summary 
statistics (mean and SE), and median (range and 95% CI) of absolute scores will be reported 
for the items and scales of the QLQ-C30 and the QLQ-LC13. The mean change of absolute 
scores from baseline (and 95% CI) will also be assessed by dosing cohort/subgroups. Line 
charts depicting the means and mean changes of subscales over time will be provided. The 
number and proportion of patients who improved, worsened, or remained stable for all of the 
symptom and functional domains, global QOL, and single items of the EORTC 
QLQ-C30 and the QLQ-LC-13 will be summarized in a table. Additional analyses may be 
performed such as repeated measures mixed-effects modeling. 
9.9. Cognitive, Mood and Suicidal Ideation and Behavior Analyses (Phase 2 only) 
For Mood assessment via the Beck Depression Inventory-II (BDI-II), frequencies and 
percentages on items capturing mood, suicidal ideation, cognitive signs as well as somatic 
signs will be summarized. 
For each of the 5-part battery test of the Cogstate assessment of Cognitive Function, the 
change from baseline scores at all post-baseline assessment will be calculated and 
summarized using descriptive statistics. 
For Suicidal Ideation and Behaviors via the Columbia Suicide Severity Rating Scale 
(C-SSRS), frequencies and percentages will be displayed for patients with suicidal ideation, 
suicidal behavior, and self-injurious behavior without suicidal intent. 
Further details are provided in the SAP. 
9.10. Japanese Patient-Only Lead In Cohort (Japan Sites Only) 
Japanese patients enrolled into the LIC will be analyzed separately from patients enrolled in 
the main part of the study. 

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9.11. Patients Receiving Crizotinib after PF-06463922 
The analysis of data on patients receiving crizotinib after PF-06463922 will focus on the 
efficacy endpoints as described in Section 2.2 (ORR, PFS, DR, TTR, OS), on AEs and 
Laboratory assessments and on Duration of Treatment. 
Efficacy Endpoints definition follow the definition of same endpoints already provided in 
Section 9.4.2 for EXP-1 through EXP-6, with the following caveats: 
• For tumor assessments, the baseline assessment will be the re-baselined assessment as 
described in Appendix 11; 
• The starting date for the calculation of PFS, TTR, and OS will be the treatment start 
date of crizotinib; 
• The analysis set definition for this population will be documented in the Statistical 
Analysis Plan. 
AEs and laboratory endpoint definitions follow the definition of the same endpoints already 
provided in Section 9.6.2, with the following caveats: 
• The baseline assessment will be the tumor assessment within 2 weeks after the last 
dose of PF-06463922, as described in Appendix 11; 
• The first dose of study medication will be defined as the treatment start date of 
crizotinib. 
9.12. Drug-drug Interaction and Holter Monitoring Study (Phase 2) 
For the evaluation of the DDI effect (potential effect of PF-06463922 on the plasma exposure 
of probe substrates), a minimum of 6 evaluable patients for each probe substrate have been 
empirically chosen. However, a sample size of 6 subjects will provide 90% CI for the 
difference between treatments of ±0.5338 on the natural logarithm scale for Cmax, with 
80% coverage probability. 
For patients participating in the DDI substudy, plasma concentration-time data for probe 
substrates (bupropion, tolbutamide, acetaminophen, or fexofenadine, and their relevant 
metabolites) in the absence of PF-06463922 on Day -2 (probe substrate alone) will be 
compared to Cycle 1 Day 15 (probe substrate in the presence of steady-state PF-06463922). 
Natural log transformed AUC24, AUCinf (if data permits), and Cmax for the probe substrates 
and their relevant metabolites will be analyzed using a mixed effect model with treatment as 
fixed effect and subject as a random effect. Estimates of the adjusted mean differences 
(Test-Reference) and corresponding 90% confidence intervals will be obtained from the 
model. The adjusted mean differences and 90% confidence intervals for the differences will 
be exponentiated to provide estimates of the ratios of adjusted geometric means 
(Test/Reference) and 90% confidence intervals for the ratios. The probe substrate alone on 
Day -2 (Treatment A) will be the Reference treatment, and the probe substrate 
co-administered with PF-06463922 on Cycle 1 Day 15 (Treatment B) will be the Test 
treatment. 

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Plasma PK parameters AUC24, AUClast, AUCinf (if data permits), Cmax, Tmax, CL/F, Vz/F and 
t1/2 for the probe substrates and PF-06463922, and AUC24, AUClast, AUCinf (if data permits), 
Cmax, Tmax, t1/2, MRCmax, MRAUCinf, and MRAUClast for relevant metabolite(s) of the probe 
substrates as well as PF-06463922 metabolite(s) will be listed and summarized descriptively 
by visit. Box whisker plots for PK parameters AUC24, AUCinf (if data permits) and Cmax, for 
the probe substrates (and their relevant metabolites) will be plotted by treatment. Plasma 
concentrations for the probe substrates, their metabolites (as appropriate), PF-06463922 and 
its metabolite will be listed and summarized descriptively by PK sampling time and 
treatment/visit. Individual subject and summary profiles (median and means) of the probe 
substrate concentration-time data will be plotted by treatment/visit. 
For summary statistics and summary 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. 
An evaluation of the effects of PF-06463922 on the PR interval will be conducted via 
continuous Holter telemetry comparing the subject’s time-matched PR interval 
(approximately 10 timepoints) with exposure of PF-06463922 following a single dose and 
again at steady state. In addition, arrhythmia analysis will be performed in these patients. 
Safety and Efficacy in patients entering the DDI and Holter monitoring study will be 
analyzed separately from the Phase 2 efficacy population, as outlined in the statistical 
analysis plan. 
9.13. Data Safety Monitoring Committee 
An external Data Safety Monitoring Committee will not be established for the study. For the 
purpose of this protocol, Pfizer procedures for periodic safety review will be applied by an 
internal safety review team with medical and statistical capabilities to review individual and 
summary data collected in the safety and clinical databases. Procedures include: 
• Surveillance for serious adverse events (SAEs) according to regulatory guidelines; 
• Discussions between the Investigators and the Sponsor of AEs and laboratory tests 
alterations seen at each dose level in an ongoing manner at regular teleconferences 
and/or meetings to determine the safety profile and benefit/risk ratio and decide if 
further enrollment is appropriate. 
9.14. Independent Central Radiological Review 
An independent core imaging laboratory will be used in Phase 2. All sites will be required to 
submit images to the core imaging laboratory for independent central review (ICR) as soon 
as they are performed at the site so that imaging scans may be read in real time. The 
requirements of submitting images will be provided to sites by the core imaging laboratory. 
For those patients who receive crizotinib after PF-06463922, submission of scans to the core 
imaging laboratory is no longer required (ie, only required during treatment with 
PF-06463922). Additionally, all sites in Phase 1 will be required to submit images to the 
core imaging laboratory for retrospective ICR. 
The independent central radiology review will be stopped when the data collection required 
for the primary and secondary endpoints is deemed sufficient. 

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Upon approval of Amendment 8, the radiologic assessments will be performed according to 
local practice. 
10. QUALITY CONTROL AND QUALITY ASSURANCE 
During study conduct, Pfizer or its agent will conduct periodic monitoring visits to ensure 
that the protocol and Good Clinical Practices (GCPs) are being followed. The monitors may 
review source documents to confirm that the data recorded on CRFs is accurate. The 
investigator and institution will allow Pfizer monitors/auditors or its agents and appropriate 
regulatory authorities direct access to source documents to perform this verification. 
The study site may be subject to review by the Institutional Review Board (IRB)/Independent 
Ethics Committee (IEC), and/or to quality assurance audits performed by Pfizer, or 
companies working with or on behalf of Pfizer, and/or to inspection by appropriate 
regulatory authorities. 
It is important that the investigator(s) and their relevant personnel are available during the 
monitoring visits and possible audits or inspections and that sufficient time is devoted to the 
process. 
11. DATA HANDLING AND RECORD KEEPING 
11.1. Case Report Forms/Electronic Data Record 
As used in this protocol, the term CRF should be understood to refer to either a paper form or 
an electronic data record or both, depending on the data collection method used in this study. 
A CRF is required and should be completed for each included patient. The completed 
original CRFs are the sole property of Pfizer and should not be made available in any form to 
third parties, except for authorized representatives of Pfizer or appropriate regulatory 
authorities, without written permission from Pfizer. 
The investigator has ultimate responsibility for the collection and reporting of all clinical, 
safety and laboratory data entered on the CRFs and any other data collection forms (source 
documents) and ensuring that they are accurate, authentic/original, attributable, complete, 
consistent, legible, timely (contemporaneous), enduring and available when required. The 
CRFs must be signed by the investigator or by an authorized staff member to attest that the 
data contained on the CRFs is true. Any corrections to entries made in the CRFs, source 
documents must be dated, initialed and explained (if necessary) and should not obscure the 
original entry. 
In most cases, the source documents are the hospital's or the physician's patient chart. In 
these cases data collected on the CRFs must match the data in those charts. 
In some cases, the CRF, or part of the CRF, may also serve as source documents. In these 
cases, a document should be available at the investigator’s site as well as at Pfizer and clearly 
identify those data that will be recorded in the CRF, and for which the CRF will stand as the 
source document. 

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11.2. Record Retention 
To enable evaluations and/or audits from regulatory authorities or Pfizer, the investigator 
agrees to keep records, including the identity of all participating patients (sufficient 
information to link records, eg, CRFs and hospital records), all original signed informed 
consent documents, copies of all CRFs, safety reporting forms, source documents, and 
detailed records of treatment disposition, and adequate documentation of relevant 
correspondence (eg, letters, meeting minutes, telephone calls reports). The records should be 
retained by the investigator according to International Conference on Harmonisation (ICH), 
local regulations, or as specified in the Clinical Study Agreement (CSA), whichever is 
longer. 
If the investigator becomes unable for any reason to continue to retain study records for the 
required period (eg, retirement, relocation), Pfizer should be prospectively notified. The 
study records must be transferred to a designee acceptable to Pfizer, such as another 
investigator, another institution, or to an independent third party arranged by Pfizer. 
Investigator records must be kept for a minimum of 15 years after completion or 
discontinuation of the study or for longer if required by applicable local regulations. 
The investigator must obtain Pfizer's written permission before disposing of any records, 
even if retention requirements have been met. 
12. ETHICS 
12.1. Institutional Review Board (IRB)/Independent Ethics Committee (IEC) 
It is the responsibility of the investigator to have prospective approval of the study protocol, 
protocol amendments, informed consent documents, and other relevant documents, eg, 
recruitment advertisements, if applicable, from the IRB/IEC. All correspondence with the 
IRB/IEC should be retained in the Investigator File. Copies of IRB/IEC approvals should be 
forwarded to Pfizer. 
The only circumstance in which an amendment may be initiated prior to IRB/IEC approval is 
where the change is necessary to eliminate apparent immediate hazards to the patients. In 
that event, the investigator must notify the IRB/IEC and Pfizer in writing immediately after 
the implementation. 
12.2. Ethical Conduct of the Study 
The study will be conducted in accordance with legal and regulatory requirements, as well as 
the general principles set forth in the International Ethical Guidelines for Biomedical 
Research Involving Human Subjects (Council for International Organizations of Medical 
Sciences 2002), Guidelines for GCP (ICH 1996), and the Declaration of Helsinki (World 
Medical Association 1996 and 2008). 
In addition, the study will be conducted in accordance with the protocol, the ICH guideline 
on GCP, and applicable local regulatory requirements and laws. 

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12.3. Patient Information and Consent 
All parties will ensure protection of patient personal data and will not include patient names 
on any Sponsor forms, reports, publications, or in any other disclosures, except where 
required by laws. 
Patient names, address, birth date and other identifiable data will be replaced by a numerical 
code consisting of a numbering system provided by Pfizer in order to de-identify the trial 
patient. 
In case of data transfer, Pfizer will maintain high standards of confidentiality and protection 
of patient personal data. 
The informed consent document must be in compliance with ICH GCP, local regulatory 
requirements, and legal requirements. 
The informed consent document(s) used during the informed consent process must be 
reviewed by the Sponsor, approved by the IRB/IEC before use, and available for inspection. 
The investigator must ensure that each study patient, or his/her legal representative, is fully 
informed about the nature and objectives of the study and possible risks associated with 
participation. 
The investigator, or a person designated by the investigator, will obtain written informed 
consent from each patient or the patient's legal representative before any study-specific 
activity is performed. The investigator will retain the original of each patient's signed 
consent document. 
12.4. Patient Recruitment 
Advertisements approved by ethics committees and investigator databases may be used as 
recruitment procedures. 
12.5. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH GCP 
In the event of any prohibition or restriction imposed (ie, clinical hold) by an applicable 
Competent Authority in any area of the World, or if the investigator is aware of any new 
information which might influence the evaluation of the benefits and risks of the 
investigational product, Pfizer should be informed immediately. 
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. 

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13. DEFINITION OF END OF TRIAL 
The End of Trial is defined as the date of the “last patient last visit” (LPLV) in the study. 
Study Completion is defined when 2/3 of OS events (deaths) have occurred. 
The End of Trial will occur after 36 months of treatment of the “last patient first visit” 
(LPFV) or upon Study Completion, whichever comes first. 
If the Study Completion occurs before the 36 month treatment period and a patient is still 
experiencing clinical benefits, a number of options for extending the study treatment will be 
considered based on the local availability of the treatment and local country laws/regulation. 
14. SPONSOR DISCONTINUATION CRITERIA 
Premature termination of this study may occur because of a regulatory authority decision, 
change in opinion of the IRB/IEC, drug safety problems, or at the discretion of Pfizer. In 
addition, Pfizer retains the right to discontinue development of PF-06463922 at any time. 
If a study is prematurely terminated or discontinued, Pfizer will promptly notify the 
investigator. After notification, the investigator must contact all participating patients and 
the hospital pharmacy (if applicable) within a time defined by Pfizer. As directed by Pfizer, 
all study materials must be collected and all CRFs completed to the greatest extent possible. 
15. PUBLICATION OF STUDY RESULTS 
15.1. Communication of Results by Pfizer 
Pfizer fulfills its commitment to publicly disclose clinical trial results through posting the 
results of studies on www.clinicaltrials.gov (ClinicalTrials.gov), the European Clinical Trials 
Database (EudraCT), and/or www.pfizer.com, and other public registries in accordance with 
applicable local laws/regulations. 
In all cases, study results are reported by Pfizer in an objective, accurate, balanced, and 
complete manner and are reported regardless of the outcome of the study or the country in 
which the study was conducted. 
www.clinicaltrials.gov 
Pfizer posts clinical trial US Basic Results on www.clinicaltrials.gov for Pfizer-sponsored 
interventional studies conducted in patients that evaluate the safety and/or efficacy of a Pfizer 
product, regardless of the geographical location in which the study is conducted. US Basic 
Results are submitted for posting within 1 year of the primary completion date for studies in 
adult populations or within 6 months of the primary completion date for studies in pediatric 
populations. 
Primary completion date is defined as the date that the final patient was examined or received 
an intervention for the purposes of final collection of data for the primary outcome, whether 
the clinical study concluded according to the prespecified protocol or was terminated. 

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EudraCT 
Pfizer posts EU Basic Results on EudraCT for all Pfizer-sponsored interventional studies that 
are in scope of EU requirements. EU Basic Results are submitted for posting within 1 year 
of the primary completion date for studies in adult populations or within 6 months of the 
primary completion date for studies in pediatric populations. 
www.pfizer.com 
Pfizer posts Public Disclosure Synopses (clinical study report synopses in which any data 
that could be used to identify individual patients has been removed) on www.pfizer.com for 
Pfizer-sponsored interventional studies at the same time the US Basic Results document is 
posted to www.clinicaltrials.gov. 
15.2. Publications by Investigators 
Pfizer has no objection to publication by Investigator of any information collected or 
generated by Investigator, whether or not the results are favorable to the Investigational 
Drug. However, to ensure against inadvertent disclosure of Confidential Information or 
unprotected Inventions, Investigator will provide Pfizer an opportunity to review any 
proposed publication or other type of disclosure before it is submitted or otherwise disclosed. 
Investigator will provide manuscripts, abstracts, or the full text of any other intended 
disclosure (poster presentation, invited speaker or guest lecturer presentation, etc) to Pfizer at 
least 30 days before they are submitted for publication or otherwise disclosed. If any patent 
action is required to protect intellectual property rights, Investigator agrees to delay the 
disclosure for a period not to exceed an additional 60 days. 
Investigator will, on request, remove any previously undisclosed Confidential Information 
(other than the study results themselves) before disclosure. 
If the study is part of a multi-centre study, Investigator agrees that the first publication is to 
be a joint publication covering all centers. However, if a joint manuscript has not been 
submitted for publication within 12 months of completion or termination of the study at all 
participating sites, Investigator is free to publish separately, subject to the other requirements 
of this Section. 
For all publications relating to the study, Institution will comply with recognized ethical 
standards concerning publications and authorship, including Section II - “Ethical 
Considerations in the Conduct and Reporting of Research” of the Uniform Requirements for 
Manuscripts Submitted to Biomedical Journals, http://www.icmje.org/index.html#authorship, 
established by the International Committee of Medical Journal Editors. 
Publication of study results is also provided for in the Clinical Study Agreement between 
Pfizer and the institution. In this section entitled Publications by Investigators, the defined 
terms shall have the meanings given to them in the Clinical Study Agreement. 

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16. REFERENCES 
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Soda M et al Identification of the transforming EML4-ALK fusion gene in 
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Rivoka K, Global survey of phosphotyrosine signaling identifies oncogenic kinases in 
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4. 
Sasaki T et al. The biology and treatment of EML4-ALK non small cell lung cancer, 
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Bergethon K et al ROS 1 Rearrangement define a unique molecular class of lung cancer. 
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Takeuchi K, Soda M, Togashi Y, Suzuki R, Sakata S, Hatano S et al. RET, ROS and 
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Camidge R et al Activity and safety of crizotinib in patients with ALK-positive non 
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Pao W Rational, biologically based treatment of EGFR-mutant non-small-cell lung 
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Doebele R et al. Mechanisms of resistance to crizotinib in patients with ALK gene 
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McGinn W, Schmidt W, Sun J, and Tripathi S. Regulatory considerations for preclinical 
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11. Yamada T et al. Paracrine receptor activation by microenvironment triggers by pass 
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12. Choi, Y. L., Soda, M., Yamashita, Y., Ueno, T., Takashima, J., Nakajima, T., et al. 
EML4-ALK Mutations in Lung Cancer That Confer Resistance to ALK Inhibitors. N 
Engl J Med 2010; 363(18):1734-39. 

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13. Otterson, G. A. Clinical characteristics of ALK+ NSCLC patients (pts) treated with 
crizotinib beyond disease progression (PD): Potential implications for management. J 
Clin Oncol 2012; (suppl; abstr 7600). 
14. Camidge, D.R. Taking Aim at ALK Across the Blood-Brain Barrier. J Thorac Oncol. 
2013; 8(4):389-90. 
15. Ou, S-H I et al. Efficacy and safety of crizotinib in patients with advanced 
ROS1-rearranged non-small cell lung cancer (NSCLC). J Clin Oncol 2013; 31:(suppl; 
:abstract 8032. 
16. Shaw AT et al. Crizotinib versus Chemotherapy in Advanced ALK-Positive Lung 
Cancer. NEJM 2013; 368: 2385-2394. 
17. Awad, M et al. Acquired Resistance to crizotinib from a mutation in CD74-ROS1. 
NEJM 2013; 368: 2395-2401. 
18. Gettinger S et al. A first in human dose finding study of the ALK/EGFR inhibitor 
AP26113 in patients with advanced malignancies. Annals Oncology 2012; 
23(suppl 9):abstract 439O. 
19. Shaw AT et al, Results of the first in human phase 1 study of the ALK inhibitor 
LDK378 in advanced malignancies. Annals Oncology 2012; 23 (suppl 9):abstract 440O. 
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Oncology 2012; 23 (suppl 9): Abst 441O. 
21. Katayama, R et al. Mechanisms of acquired crizotinib resistance in ALK-rearranged 
lung cancers. Sci.Transl. Med. 2012; 3: 120ra17. 
22. PF-06463922 Investigator’s Brochure 2013. 
23. Vernersson E, Khoo NK, Henriksson ML, et al. Characterization of the expression of 
the ALK receptor tyrosine kinase in mice. Gene Expr Patterns 2006;6:448-61. 
24. Iwahara T, Fujimoto J, Wen D, et al. Molecular characterization of ALK, a receptor 
tyrosine kinase expressed specifically in the nervous system. Oncogene 
1997;14:439-449. 
25. Bilsland JG, Wheeldon A, Mead A, et al. Behavioral and neurochemical alterations in 
mice deficient in anaplastic lymphoma kinase suggest therapeutic potential for 
psychiatric indications. Neuropsychopharmacology 2008;33:685-700. 
26. Lynch MA. Long-term potentiation and memory. Physiol Rev 2004;84:87-136. 
27. Yamada K and Nabeshima T. Brain-derived neurotrophic factor/TrkB signaling in 
memory processes. J Pharmacol Sci 2003; 91(4):267–70. 

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28. Banks P et al. Practice guidelines in acute pancreatitis. American J Gastroenterology 
2006; 101: 2379-2400. 
29. Lankisch PG et al. Hyperamylasemia and/or hyperlipasemia: Incidence and underlying 
causes in hospitalized patients with non pancreatic disease. Scandinavian J 
Gastroenterology 2009; 44: 237-241. 
30. Srivastava R et al. Hyperamylasemia: not the usual suspects. BMJ 2005; 331: 890-891. 
31. Weickhardt et al. Symptomatic Reduction in Free Testosterone Levels Secondary to 
Crizotinib Use in Male Cancer Patients. Cancer 2013 Article first published online: 12 
APR 2013DOI: 10.1002/cncr.28089. 
32. Long G et al. Dabrafenib in patients with Val600GLu or Val600Lys BRAF-mutant 
melanoma metastatic to the brain (BREAK-MB): a multicentre, open-label, Phase 2 
trial. Lancet Oncology 2012; 13:1087-1095. 
33. NK Aaronson et al. The European Organization for Research and Treatment of Cancer 
QLQ-C30: a quality-of-life instrument for use in international clinical trials in 
oncology. J Natl Cancer Inst 85:365-76, 1993. 
34. Fayers P et al. Quality of Life Research within the EORTC – The EORTC QLQ-C30, 
on behalf of the EORTC Quality of Life Group. Eur J Cancer 38:125-133, 2002. 
35. Bergman, B et al. The EORTC QLQ-LC13: a modular supplement to the EORTC Core 
Quality of Life Questionnaire (QLQ-C30) for use in lung cancer clinical trials. EORTC 
Study Group on Quality of Life. Eur J Cancer 30A:635-42, 1994. 
36. Bottomley A, Efficace F, Thomas R, Vanvoorden V, Ahmedzai S. Health related 
quality of life in non-small cell lung cancer: Methodological issues in randomised 
controlled trials. Journal of Clinical Oncology 2003;21(15):2989-2992. 
37. Folstein M et al. Mini-Mental State a practical method for grading the cognitive state of 
patients for the clinican. Journal of Psychiatric Research 1975; 12 (3): 189-198. 
38. Mystakidou K et al. Brief cognitive assessment of cancer patients: evaluation of the 
Mini-Mental State Examination (MMSE) psychometric properties. Psycho-oncology 
2007; 16: 352-357 
39. Eisenhauer EA et al, New response evaluation criteria in solid tumours: revised 
RECIST guideline (version 1.1). Eur J Cancer 45: 228-27, 2009. 
40. O’Brien, P. C. and Fleming, T. R. A Multiple Testing Procedure for Clinical Trials. 
Biometrics 1979; 35: 549–556. 
41. USPI for Midazolam Hydrochloride Syrup, Paddock Laboratories, Inc, Minneapolis, 
MN, 55472 (06-08). 

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42. Investigator’s Brochure, Crizotinib. 
43. Posner K, Brown GK, et al. The Columbia–Suicide Severity Rating Scale: Initial 
Validity and Internal Consistency Findings from Three Multisite Studies With 
Adolescents and Adults. Am J Psychiatry 2011; 168: 1266-1277. 
44. Cogstate Ltd, New Haven, NJ. 
45. Zou, H, et al. 2015, Cancer Cell 28, 70-81, July 13, 2015. 
46. Katayama, R., Shaw, A.T., Khan, T.M., Mino-Kenudson, M., Solomon, B.J., Halmos, 
B., Jessop, N.A., Wain, J.C., Yeo, A.T., Benes, C., et al. (2012). Mechanisms of 
acquired crizotinib resistance in ALK-rearranged lung cancers. Sci. Transl. Med. 4, 
120ra17. 
47. Kogita, A., et al. (2015). Activated MET acts as a salvage signal after treatment with 
alectinib, a selective ALK inhibitor, in ALK-positive non-small cell lung cancer. 
International Journal of Oncology. 10.3892/ijo.2014.2797. 
48. Isozak, H., et al. Acquired reistance to a new ALK inhibitor, alectinib in lung cancer. 
Annals of Oncology 25 (Supplement 4): iv546–iv563, 2014. 
doi:10.1093/annonc/mdu358.15. 
49. Nada A, Gintant GA, Kleiman R, et al. The evaluation and management of drug effects 
on cardiac conduction (PR and QRS intervals) in clinical development. Am Heart J 
2013;165:489-500. 

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Appendix 1. Phase 1 Required Laboratory Assessments 
 
Phase 1 Dose Escalation Single Agent 
Hematology 
Chemistry 
Coagulation 
Lipids 
Urinalysis 
Pregnancy Test 
Hemoglobin 
ALT 
PT or INR 
Total Cholesterol 
Urine dipstick for urine protein: 
If positive collect 24-hr and 
microscopic (Reflex Testing) 
Serum from female 
patients of 
childbearing potential 
Platelets 
AST 
PTT 
LDL 
WBC 
Alk Phos 
HDL 
Absolute Neutrophils 
Sodium 
Triglycerides 
Absolute Lymphocytes 
Potassium 
Urine dipstick for urine blood: If 
positive collect a microscopic 
(Reflex Testing) 
Absolute Monocytes 
Magnesium 
Absolute Eosinophils 
Chloride 
Absolute Basophils 
Total Calcium 
Total Bilirubin * 
BUN or Urea 
Creatinine 
Uric Acid 
Glucose - 
Albumin 
Phosphorous or Phosphate 
Serum total amylase 
(pancreatic isoenzyme 
required if serum total 
amylase not within normal 
limits per local institutional 
ranges). 
Serum lipase 
*For potential Hy'sLlaw cases, in addition to repeating AST and ALT, laboratory tests should include albumin, creatine kinase, total bilirubin, direct and 
indirect bilirubin, gamma-glutamyl transferase, prothrombin time (PT)/INR, and alkaline phosphatase. 

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Appendix 2. Phase 2 Required Laboratory Assessments 
 
Phase 2 Laboratory Assessments 
Hematology 
Chemistry 
Coagulation 
Lipids 
Urinalysis 
Pregnancy Test 
Hemoglobin 
ALT 
PT or INR 
Total Cholesterol 
Urine dipstick for urine protein: 
If positive collect 24-hr and 
microscopic (Reflex Testing) 
Serum from female patients of 
childbearing potential 
Platelets 
AST 
PTT 
LDL 
WBC 
Alk Phos 
HDL 
Absolute Neutrophils 
Sodium 
Triglycerides 
Absolute Lymphocytes 
Potassium 
Urine dipstick for urine blood: 
If positive collect a 
microscopic (Reflex Testing) 
Hypogonadism blood 
sampling between 
08:00-11:00 in male patients 
only 
Absolute Monocytes 
Magnesium 
Total Testosterone (TT) 
Absolute Eosinophils 
Chloride 
Free Testosterone (Free T) 
Absolute Basophils 
Total Calcium 
Lutenizing Hormone(LH) 
Total Bilirubin * 
Follicle Stimulating Hormone 
(FSH) 
BUN or Urea 
Sex Hormone Binding Globulin 
(SHBG) 
Creatinine 
Prolactin 
Uric Acid 
Dehydroepiandrosterone 
sulphate (DHEA-s) 
Glucose (non-fasted) 
Estradiol 
Albumin 
Phosphorous or 
Phosphate 
Serum total amylase 
Serum lipase 
*For potential Hy's Law cases, in addition to repeating AST and ALT, laboratory tests should include albumin, creatine kinase, total bilirubin, direct and 
indirect bilirubin, gamma-glutamyl transferase, prothrombin time (PT)/INR, and alkaline phosphatase. 

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Appendix 3. RECIST (Response Evaluation Criteria in Solid Tumors) v1.1 Modified to 
Include Assessment of CNS Metastases 
At baseline, individual tumor lesions will be categorized by the investigator as either 
measurable or not, according to the criteria summarized below.39 
Measurable Lesions 
Lesions that can be accurately measured in at least one dimension (longest diameter in the 
plane of measurement is to be recorded) with a minimum size of: 
• 10 mm for all lesions including CNS lesions, but excluding lymph nodes and assessed 
by CT scan (CT scan slice thickness no greater than 5 mm). 
• 5 mm for CNS lesions provided gadolidium contrast enhanced MRI is perfomed 
with contingent slices of 1mm. 
• 10 mm for lesions assessed clinically by caliper measurement (lesions which cannot 
be accurately measured with calipers should be recorded as non-measurable). 
• 20 mm for lesions assessed by chest X-ray. 
• 15 mm in short axis for lymph nodes when assessed by CT scan (CT scan slice 
thickness recommended to be no greater than 5 mm). 
Non-Measurable Lesions 
Non-measurable lesions include small lesions (longest diameter <10 mm or pathological 
lymph nodes with a 10 but <15 mm short axis) as well as truly non-measurable lesions. 
Truly non-measurable lesions include: leptomeningeal disease, ascites, pleural or pericardial 
effusion, inflammatory breast disease, lymphangitic involvement of skin or lung, abdominal 
masses identified by physical exam and not measurable by reproducible imaging techniques. 
Nodes that have a short axis <10 mm are considered non-pathological and should not be 
recorded or followed. 
Special Considerations Regarding Specific Lesions 
Bone lesions: 
• Bone scan, PET scan or plain films are not considered adequate imaging techniques 
to measure bone lesions. However, these techniques can be used to confirm the 
presence or disappearance of bone lesions. 
• Lytic bone lesions or mixed lytic-blastic lesions, with identifiable soft tissue 
components, that can be evaluated by cross sectional imaging techniques such as CT 
or MRI can be considered as measurable lesions if the soft tissue component meets 
the definition of measurability described above. 

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• Blastic bone lesions are non-measurable. 
Cystic lesions: 
• Lesions that meet the criteria for radiographically defined simple cysts should not be 
considered as malignant lesions (neither measurable nor non-measurable) since they 
are, by definition, simple cysts. 
• ‘Cystic lesions’ thought to represent cystic metastases can be considered as 
measurable lesions, if they meet the definition of measurability described above. 
However, if non-cystic lesions are present in the same patient, these are preferred for 
selection as target lesions. 
Lesions with prior local treatment: 
• Tumor lesions situated in a previously irradiated area, or in an area subjected to other 
loco-regional therapy, are usually not considered measurable unless there has been 
demonstrated progression in the lesion. 
Solitary lesions: 
If a measurable disease is restricted to a solitary lesion, its neoplastic nature should be 
confirmed by cytology/histology. 
Recording Tumor Measurements 
All measurable lesions up to a maximum of 2 lesions per organ and up to 5 in total and 
representative of all involved organs should be identified as target lesions and measured and 
recorded at baseline and at the stipulated intervals during treatment. Exception to this rule 
is in the presence of CNS metastases 5 mm in diameter assessed by gadolidium 
contrasted MRI with slices of 1 mm; up to 5 CNS lesions will be permitted in addition 
to 5 extracranial lesions previously noted.32 Target lesions should be selected on the basis 
of their size (lesions with the longest diameters) and their suitability for accurate repetitive 
measurements (either by imaging techniques or clinically). 
The longest diameter will be recorded for each target lesion. The sum of the longest 
diameter of all target lesions will be calculated and recorded as the baseline sum diameter to 
be used as reference to further characterize the objective tumor response of the measurable 
dimension of the disease during treatment. 
One exception to the above described approach is related to pathological lymph nodes. 
Pathological lymph nodes are defined as measurable lesions and may be identified as target 
lesions if the criterion of a short axis of 15 mm by CT scan is met. Only the short axis of 
these nodes will contribute to the baseline sum. Nodal size is normally reported as two 
dimensions in the plane in which the image is obtained (for CT scan this is almost always the 
axial plane; for MRI the plane of acquisition may be axial, sagittal or coronal). The smaller 
of these measures is the short axis. 

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

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

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If the positive FDG-PET at follow-up is not confirmed as a new site of disease on CT, 
additional follow-up CT scans are needed to determine if there is truly progression occurring 
at that site (if so, the date of PD will be the date of the initial abnormal FDG-PET scan). 
If the positive FDG-PET at follow-up corresponds to a pre-existing site of disease on CT that 
is not progressing on the basis of the anatomic images, this is not PD. 
Confirmation of Tumor Response 
Confirmation of response will be required at least 4 weeks after the initial response is 
observed. 
Determination of Overall Response by the RECIST v1.1 
When both target and non-target lesions are present, individual assessments will be recorded 
separately. The overall assessment of response will involve all parameters as depicted in 
Table 20. 
Table 20. Response Evaluation Criteria in Solid Tumors 
 
Target lesions 
Non-target lesions 
New 
Lesions 
Overall 
response 
CR 
CR 
No 
CR 
CR 
Non-CR/non-PD 
No 
PR 
CR 
Not evaluated 
No 
PR 
PR 
Non-PD or 
not all evaluated 
No 
PR 
SD 
Non-PD or 
not all evaluated 
No 
SD 
Not all 
evaluated 
Non-PD 
No 
NE 
PD 
Any 
Yes or No 
PD 
Any 
PD 
Yes or No 
PD 
Any 
Any 
Yes 
PD 
CR = complete response, PR = partial response, SD = stable disease, 
PD = progressive disease, and NE = inevaluable. 
 
Best Overall Response 
The best overall response is determined once all the data for the patient is known. Best 
response in trials in which confirmation of complete or partial response is not required 
(ie, randomized trails) is defined as the best response across all time points (for example, a 
patient who has SD at first assessment, PR at second assessment, and PD on last assessment 
has a best overall response of PR). When SD is believed to be the best response, it must also 
meet the protocol specified minimum time from baseline. If the minimum time is not met 
when SD is otherwise the best time point response, the patient’s best response depends on the 
subsequent assessments. For example, a patient who has SD at first assessment, PD at 
second and does not meet minimum duration for SD, will have a best response of PD. The 
same patient lost to follow-up after the first SD assessment would be considered inevaluable. 

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For CR and PR, confirmation is required at least 4 weeks after the initial response is 
observed. Therefore, CR and PR may only be claimed as the best overall response provided 
this confirmation is met. 
Patients with a global deterioration of health status requiring discontinuation of treatment 
without objective evidence of disease progression at that time should be reported as ‘global 
deterioration of health status’. Every effort should be made to document objective 
progression even after discontinuation of treatment. Global deterioration of health status is 
not a descriptor of an objective response: it is a reason for stopping study therapy. The 
objective response status of such patients is to be determined by evaluation of target and 
non-target lesions. 
In some circumstances it may be difficult to distinguish residual disease from normal tissue. 
When the evaluation of CR depends upon this determination, it is recommended that the 
residual lesion be investigated (fine needle aspirate/biopsy) before assigning a status of 
complete response. FDG-PET may be used to upgrade a response to a CR in a manner 
similar to a biopsy in cases where a residual radiographic abnormality is thought to represent 
fibrosis or scarring. The use of FDG-PET in this circumstance should be prospectively 
described in the protocol and supported by disease specific medical literature for the 
indication. However, it must be acknowledged that both approaches may lead to false 
positive CR due to limitations of FDG-PET and biopsy resolution/sensitivity. 

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Appendix 4. ECOG Performance Status 
Grade ECOG 
0 
Fully active, able to carry on all pre-disease activities 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 or office work. 
2 
Ambulatory and capable of all selfcare but unable to carry out any work activities. Up 
and about more than 50% of waking hours. 
3 
Capable of only limited selfcare, confined to bed or chair more than 50% of waking 
hours. 
4 
Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair. 
5 
Dead. 

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Appendix 5. Bone Marrow Reserve in Adults 
 
Bone 
Relative red 
bone marrow 
content (%) 
Cranium 
7.3 
Mandible 
0.8 
Scapulae 
6.4 
Clavicles 
1.4 
Sternum 
1.8 
Ribs 
15.8 
Cervical vertebrae 
2.2 
Thoracic vertebrae 
11.8 
Lumbar vertebrae 
9.3 
Sacrum 
6.5 
Pelvis 
19.7 
Femurs (upper half) 
11.1 
Humeri (upper half) 
5.8 
Total skeleton 
100.0 
Adapted from: 
Zankle M, Wittman A. 
The adult male voxel model "Golem" segmented from whole body CT patient data. 
Rad Environ Biophysics 40:153 62, 2001 

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Appendix 6. EORTC QLQ-C30 Questionnaire 
 

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Appendix 7. EORTC QLQ-LC13 Questionnaire 
 

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Appendix 8. Mini Mental State Examination 
For copyright reasons, the MMSE may not be reproduced here. The tool and instructions 
may be found in the following publication: 
Folstein M et al. Mini-Mental State a practical method for grading the cognitive state of 
patients for the clinican. Journal of Psychiatric Research 1975; 12 (3):189-198. 
The Forms and Instructions will be provided as paper copies to the participating 
investigational sites in the Site Study Manuals. 

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Appendix 9. Japanese Patient-Only Lead-In Cohort (LIC) Schedule of Assessments 
Note: The current table is no longer applicable after the approval of Amendment 8, please refer to Table 1. 
 
CYCLE 1 
(21 days) 
CYCLE 2 
(21 days) 
CYCLES 3 –25 
(Up to Month 18) 
(21 days) 
CYCLES >25 
(Months ˃18) 
(21 days) 
Protocol Activity 
Screen1 
(28 days) 
Day 1 
Day 8 
Day 15 
Day 1 
Day 1 
Day 1 of Every 
Other Cycle 
End of 
Treatment25 
Follow- Up24 
Visit Window (days) 
N/A 
1 
1 
1 
2 
2 
2 
2 
±7 
Informed consent2 
X 
Tumor history 
X 
Medical history 
X 
Physical examination 
X 
(X) 
X 
X 
X 
Baseline signs and symptoms3 
X 
Height 
X 
Weight 
X 
X 
X 
X 
X 
Vital signs4 
X 
X 
X 
X 
X 
X 
X 
X 
Performance status5 
X 
X 
X 
X 
X 
X 
Contraception check (as 
appropriate) 
X 
X 
X 
X 
Laboratory 
Hematology6 
X 
(X) 
X 
X 
X 
X 
X 
X 
Blood Chemistry7 
X 
(X) 
X 
X 
X 
X 
X 
X 
Lipids8 
X 
(X) 
X 
X 
X 
X 
X 
X 
Hypogonadism (male patients)9 
X 
X 
X 
C5D1 and Q 4 cycles 
thereafter 
Q 4 cycles 
X 
Coagulation10 
X 
(X) 
X 
Urinalysis11 
X 
(X) 
X 
X 
X 
Pregnancy test12 
X 
(X) 
X 
X 
X 
X 
(12 lead) ECG13 
X 
X 
X 
X 
X 
X 
(up to Cycle 5) 
X 
Pulse Oximetry27 
X 
X 
X 
X 
X 
X 
(up to Cycle 5) 
X 
Chest X-ray or Chest CT28 
X 
LVEF assessment 
(Echocardiogram or MUGA)26 
X 
X 
X 
Every 4 cycles 
X 
Registration and Treatment 
Registration14 
(X) 
PF-06463922 Treatment15 
Once a day or twice a day, continuously 

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CYCLE 1 
(21 days) 
CYCLE 2 
(21 days) 
CYCLES 3 –25 
(Up to Month 18) 
(21 days) 
CYCLES >25 
(Months ˃18) 
(21 days) 
Protocol Activity 
Screen1 
(28 days) 
Day 1 
Day 8 
Day 15 
Day 1 
Day 1 
Day 1 of Every 
Other Cycle 
End of 
Treatment25 
Follow- Up24 
Visit Window (days) 
N/A 
1 
1 
1 
2 
2 
2 
2 
±7 
Tumor Assessments 
CT or MRI Scan or Equivalent16 
X 
X and then every 
6 weeks 1 week 
Every 12 weeks ± 
1 week 
(X) 
(X) 
Cerebrospinal fluid if 
leptomenigeal/carcinomatous 
meningitis [LM/CM]disease is 
present17 
X 
As indicated 
As indicated 
Other Clinical Assessments 
Adverse Events18 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant medications and 
non drug supportive 
interventions19 
X 
X 
X 
X 
X 
X 
EORTC QLQ-C30, QLQ-LC1323 
X 
X 
X 
X 
X 
Cognitive Assessment29 
X 
X 
X 
X up to Cycle 6 and 
then D1 of every 
other cycle 
X 
X 
Mood Assessment30 
X 
X 
X 
X up to Cycle 6 and 
then D1 of every 
other cycle 
X 
X 
Suicidal Ideation and Behavior31 
X 
X 
X 
X up to Cycle 6 and 
then D1 of every 
other cycle 
X 
X 
Survival Follow-up 
X 
Other Samples 
Archival Tumor Tissue 
Specimen20 
X 
Blood Specimens for Circulating 
Nucleic Acid (CNA) Profiling21 
X 
X 
X 
Banked Biospecimen22 
X 
Footnotes (X) refer to specific footnote when the measurement may be optional /repeat measurement might not be required. For example, if a patient will not have the 
Lead-In (Day -7) Visit, some assessments may be required on Cycle 1 Day 1 instead of Day -7 and vise versa. 

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1. 
Screening: To be obtained within 28 days prior to registration. 
2. 
Informed Consent: Must be obtained prior to undergoing any study-specific procedures not considered standard of care. 
3. 
Baseline Signs & Symptoms: Patients will be asked about any signs and symptoms experienced within the 14 days prior to study entry. Worsening Baseline signs and 
symptoms will be recorded on the Adverse Events CRF page. 
4. 
Vital signs: blood pressure and pulse rate to be recorded in sitting position. 
5. 
Performance Status: use ECOG – see Appendix 4. 
6. 
Hematology: No need to repeat on C1D1 if baseline assessment performed within 7 days prior to that date. See Assessments section for Laboratory Tests in Appendix 2. For 
those visits after C1D1, hematology labs may be done within 72 hours of dosing with results checked prior to dosing. 
7. 
Blood Chemistry: No need to repeat on C1D1 if baseline assessment performed within 7 days prior to that date. See Assessments section for Laboratory Tests in 
Appendix 2. For those visits after C1D1, chemistry labs may be done within 72 hours of dosing with results checked prior to dosing. 
8. 
Lipids: No need to repeat on C1D1 if baseline assessment performed within 7 days prior to that date. See Assessments section for Laboratory Tests in Appendix 2. For those 
visits after C1D1, lipid labs may be done within 72 hours of dosing with results checked prior to dosing. 
9. 
Hypogonadism Laboratory Test: to be performed in male patients only. The required blood tests are reported in Appendix 2. Blood draws MUST be done between 
08.00-11.00 AM. Should a decrease of 25% from baseline be observed in total testosterone or free testosterone a repeat laboroatory analysis of both these parameters must 
be performed at the next clinical visit to confirm hypogonadism. 
10. Coagulation: No need to repeat on C1D1 if baseline assessment performed within 7 days prior to that date. See Assessments section for Laboratory Tests in Appendix 2. 
For those visits after Cycle 1 Day 1, coagulation labs may be done within 72 hours of dosing with results checked prior to dosing. 
11. Urinalysis: Dipstick is acceptable. Microscopic analyses if dipstick abnormal. No need to repeat on C1D1 if baseline assessment performed within 7 days prior to that date. 
See Assessments section for Laboratory Tests in Appendix 2. 
12. Serum Pregnancy Test: For female patients of childbearing potential, a serum or urine pregnancy test, with sensitivity of at least 25 mIU/mL, will be performed on two 
occasions prior to starting study therapy - once at the start of screening and once at the baseline visit, immediately before investigational product administration. Pregnancy 
tests will also be routinely repeated at every cycle during the active treatment period (every other cycle beyond 18 months), at the end of study therapy and additionally 
whenever one menstrual cycle is missed or when potential pregnancy is otherwise suspected. Additional pregnancy tests may also be undertaken if requested by IRB/IECs or 
if required by local regulations. 
13. Triplicate 12-lead ECGs: At each time point, 3 consecutive 12-lead ECGs will be performed approximately 2 minutes apart to determine mean QTc interval. ECGs will be 
collected as follows: a) at Screening, b) Cycle 1 Day 1 pre-dose and 1 hr, 2 hr and 4 hr post-dose), c) Cycle 1 Day 8 and Day 15 at pre-dose, 1 hr and 2 hr post dose, 
d) Cycles 2-5 Day 1 at pre-dose, 1 hr and 2 hrs post dose and e) End of Treatment. If at any of these timepoints the mean QTc is prolonged (501 msec), the ECGs should be 
re-evaluated by a qualified person at the institution for confirmation. Additional triplicate ECGs may be performed as clinically indicated. 
When an ECG and PK sample are scheduled at the same time, ECG assessments should be performed prior to PK sample such that the PK sample is collected at the nominal 
time (but regardless, the exact time of ECG assessment and PK collection should always be recorded). 
14. Registration: Registration will be within 2 days prior to lead-in or study treatment start. 
15. Trial Treatment: described in the Study Treatments section. 

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16. Tumor Assessment: Tumor assessments will include all known or suspected disease sites. CT or MRI scans of Chest Abdomin Pelvis [CAP] and MRI of the brain will be 
performed at screening. Gadolinium contrast enhanced MRI for must be used for assessment of CNS lesions with contingent slices of 1 mm for lesions 5 mm – 10 mm in 
size, 5mm for lesions greater than 10mm. Bone scans (or bone MRI if preferred by investigator) will be performed at baseline for all patients and repeated every 12 weeks on 
study only if evidence of bone metastases are observed at baseline. For patients who are without documented disease progression, CT and MRI scans to be done at every 
6 weeks 1 week up to approximately 18 months, and then every 12 weeks ±1 week beyond 18 months, and responses will be confirmed 4 weeks later (RECIST v1.1) until 
documented progression of disease. For patients with bone involvement at Screening, CT or MRI or other appropriate imaging for bone assessment will be done every 
6 weeks 1 week up to approximately 18 months, and then every 12 weeks ±1 week beyond 18 months (in addition to the every 12 week bone scan or bone MRI for detection 
of new disease) and responses will be confirmed 4 weeks later (RECIST v1.1) until documented progression of disease. For patients who have documented disease 
progression, but are still receiving treatment with PF-06463922, tumor assessments should be done according to local institutional standard of care. For all tumor 
assessments, the method of assessment used at baseline should be the same method used throughout the study. Every effort should be made to maintain the assessment 
scheduling relative to Cycle 1 Day 1 especilaly if there are dosing cycle interruptions due to toxicities. Tumor assessment should be repeated at the end of treatment and study 
visits if more than 6 weeks have passed (more than 12 weeks beyond month 18) since the last evaluation. Tumor assessments will continue until progression of disease or a 
new anti-cancer therapy has commenced. 
17. Cerebrospinal fluid (CSF) CSF analysis will not be required unless patients have suspected or confirmed leptomeningeal carcinomatosis not visualised on MRI. When 
applicable, CSF sample will be collected at Screening (optional CSF collection post-Screening). See PK assessments for PF-06463922 CSF concentration sampling 
(optional). 
18. Adverse Event (AE) Assessments: Adverse events should be documented and recorded at each visit using NCI CTCAE version 4.03. Patients must be followed for AEs for 
28 days after the last treatment administration or until all drug related toxicities have resolved, whichever is later; or earlier than 28 days should the patient commence another 
anti-cancer therapy in the meantime. For SAEs, the active reporting period to Pfizer or its designated representative begins from the time that the patient provides informed 
consent, which is obtained prior to the patient’s participation in the study, ie, prior to undergoing any study-related procedure and/or receiving investigational product, through 
and including 28 calendar days after the last administration of the investigational product. Serious adverse events occurring to a patient after the active reporting period has 
ended should be reported to the Sponsor if the investigator becomes aware of them; at a minimum, all serious adverse events that the investigator believes have at least a 
reasonable possibility of being related to study drug are to be reported to the Sponsor. 
19. Concomitant Medications and Non-Drug Supportive Interventions: All concomitant medications and non-drug supportive interventions should be recorded in the CRF. 
20. Archival Tumor Tissue Specimens: All patients will provide a formalin-fixed paraffin embedded (FFPE) archival tumor specimen, specifically a FFPE tissue block that 
contain sufficient tissue to generate at least 6 (preferably 12) unstained slides, each with tissue sections that are 5 microns thick, or at least 6 (preferably 12) unbaked glass 
slides, each containing an unstained 5 micron FFPE tissue section if FFPE tissue block cannot be submitted. If an archival tumor tissue sample is not available, a de novo 
tumor specimen must be obtained. Specimens will be sent to the Sponsor-designated central laboratories for assessment of biomarkers potentially associated with sensitivity 
and/or resistance to PF-06463922 (eg, ALK mutations, mutations/copy number variation of candidate genes, expression and/or phosphorylation of candidate proteins, etc); for 
ROS1+ NSCLC patients specimens will be sent to the Sponsor-designated central laboratory for ROS1 status confirmation. 
21. Blood Specimens for Circulating Nucleic Acid (CNA) Profiling: 10 ml blood specimen optimized for plasma preparation for nucleic acid analysis (eg, circulating free 
DNA (cfDNA) or RNA (cfRNA)) will be collected at screening, at the end of Cycle 2 matching the first tumor restaging (in practical terms, this may be C3D1 pre-dose) and 
at end of treatment. Details for handling of these specimens including processing, storage, and shipment will be provided in the Study Manual. 
22. Banked Biospecimens: Unless prohibited by local regulations, a blood sample (Prep D1: 4 mL K2 EDTA whole blood collection optimized for DNA analysis), retained for 
pharmacogenomic analyses, will be collected at screening. 
23. EORTC QLQ-C30 and QLQ-LC13: Patients must complete all EORTC QLQ-C30 and QLQ-LC13 self-assessment questionnaires in the clinic at the specified time points 
prior to dosing. At Cycle 1 Day 1 site staff (eg, site coordinators) should instruct patients that the assessment should be completed without help from friends or family 
members and also recommend that this assessment be completed in the morning. All scheduled assessments of the EORTC QLQ-C30 and QLQ LC13 cannot be taken home 
and must be completed in the clinic prior to any other study or medical procedures. 

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24. Follow up: At least 28 days, and no more than 35 days after discontinuation of treatment patients will return to undergo review of concomitant medications and assessment 
for resolution of any treatment-related toxicity. Patients continuing to experience toxicity at this point following discontinuation of treatment will continue to be followed at 
least every 4 weeks until resolution or determination, in the clinical judgment of the Investigator, that no further improvement is expected. Patients discontinuating treatment 
for reasons other than progression of disease will continue to perform tumor assessments until PD or a new anti-cancer therapy is commenced. Bimonthly survival followup 
after PD or new anti-cancer therapy has commenced will be performed (telephone contact is acceptable). 
25. End of Treatment Visit: Obtain these assessments if not completed in the last week (last 6 weeks for tumor assessments if during first 18 months, then last 12 weeks if 
beyond month 18). 
26. LVEF Assessment: Echocardiogram or MUGA will be performed at Screening, before dosing at Day 1 Cycle 2, before dosing at Day 1 Cycle 3, before dosing at 
Day 1 Cycle 5 and every two cycles thereafter up to approximately 18 months, and then every 4 cycles thereafter, and at the End of Treatment visit (a 2 days time window is 
allowed at all time-points applicable at the discretion of the investigator). The same method should be used at each time point. 
27. Pulse Oximetry: Pulse oximetry will be performed within 14 days prior to the first dose of study treatment, and during treatment as described in the table above. Pulse 
oximetry should be repeated if clinically indicated. 
28. Chest X-ray or Chest CT: Chest X-ray or Chest CT will be performed within 14 days prior to the first dose of study drug. Chest X-ray or CT should be repeated if clinically 
indicated and at the discretion of the investigator. Patients who have had a CT scan including chest for the purpose of tumor assessment for this study will not need to be 
repeated at baseline. 
29. Cognitive Assessment: A computerized cognitive test compromised of verbal learning, psychomotor function, attention and memory will be administed to patients prior to 
study drug dosing. This test will take approximately 10-20 minutes to complete and will be administered via a qualified site personnel. A practice test will be performed at 
Screening and a baseline test will be done prior to dosing on C1D1and then prior to dosing on Day 1 of Cycle 2 –Cycle 6 (±1 week). After C6D1, this will be administed 
prior to dosing on D1 of every other cycle ±1 week (ie, C8D1, C10D1, etc.). 
30. Mood Assessment: An assessment of mood via the Beck Depression Inventory-II (BDI-II) scale will be administered to patients prior to study drug dosing. The assessment 
will be given prior to dosing on C1D1 and then prior to dosing on Day 1 of Cycle 2 –Cycle 6 (±1 week). After C6D1, this will be administed prior to dosing on D1 of every 
other cycle ±1 week (ie, C8D1, C10D1, etc.). 
31. Suicidal Ideation and Behavioral Assessment: An assessment of suicidal ideation via the Columbia Suicide Severity Rating Scale (C-SSRS) will be administered to patients 
prior to dosing on C1D1 and then prior to dosing on Day 1 of Cycle 2 –Cycle 6 (±1 week). After C6D1, this will be administed prior to dosing on D1 of every other cycle 
±1 week (ie, C8D1, C10D1, etc.). 

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Japanese Patient-Only Lead-In Cohort (LIC) Pharmacokinetic Sampling Schedule 
 
CYCLE 1 
(21 days) 
CYCLE 2-5 
(21 days) 
CYCLE 6, Cycle 8 and 
Cycle 10 
(21 days) 
Protocol Activity 
Day 1 
Day 8 
Day 15 
Day 1 
Day 1 
Visit Window 
1 
1 
1 
2 
2 
All Patients 
Plasma sampling for 
PF-06463922 PK1 
X 
X 
X 
X 
X 
PF-06463922 metabolite profiling 
blood sample2 
X 
Cerebrospinal fluid (CSF) for 
PF-06463922 concentration (optional)3 
Any time during steady state ideally 4-6 hrs and 8-9 hrs post-dose 
Blood sample (when CSF for 
PF-06463922 is collected)4 
Same time as CSF PF-06463922 concentration sample collected 
Footnotes 
1. 
PF-06463922 PK Sampling (Japanese LIC patients): Blood samples will be collected on Cycle 1 Day 1 and Cycle 1 Day 15 at pre-dose, 0.5, 1, 2,3, 4, 6, 8, 9 and 24 hours 
post dose. On Cycle 1 Day 8, a blood sample will be collected at pre-dose, 1, 2 and 4 hrs post-dose. Cycles 2-5: Pre-dose, 1 and 2 hrs post dose. Day 1 of Cycle 6 and Day 
1 of Cycles 8 and 10: Pre-dose. Patients will be hospitalized for PK sampling for at least the first two days on Cycle 1 Day 1 and Cycle 1 Day 15. 
2. 
PF-06463922 Metabolite profiling (Japanese LIC patients): Blood samples will be collected at steady-state, Cycle 1 Day 15: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, and 24 hrs 
post-dose. 
3. 
CSF PF-06463922 Concentration Sample (Optional): If a patient undergoes a lumber puncture, a sample of CSF should be collected for exploratory analysis of 
PF-06463922 concentration, if possible. If scheduling permits, one CSF sample should be taken between 4 and 6 hours post dose. If it is possible to take a second sample, 
collection should be between 8 and 9 hours post-dose. 
4. 
A blood sample for PK analysis should be collected at approximately the same time as the CSF PF-06463922 concentration sample. 

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Appendix 10. Safety Review Process for Japanese Only Patient LIC 
Following 1 cycle (21 days) of treatment, a safety review will be performed by Japanese 
investigators, Pfizer Japan, and the global Pfizer Team to determine Japan site participation 
in Phase 2. Emerging Phase 1 safety/PK data in Western patients will also be used as a 
reference. 

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Appendix 11. Patients Receiving Crizotinib Following PF-06469322 
Patients in EXP-1 who discontinue PF-06463922 for reasons other than withdrawal of 
consent may be eligible to receive single-agent crizotinib. At the time of 
PF-06463922 discontinuation, patients will undergo a brief Screening period to ensure 
inclusion and exclusion criteria are met and required assessments are performed. Patients 
may initiate crizotinib within 5 days after discontinuing treatment with PF-06463922. In 
situations of disease-related tumor flare, patients may initiate crizotinib sooner per 
investigator discretion for appropriate and necessary patient management. The last tumor 
assessment performed prior to initiating treatment with crizotinib will be considered the 
baseline tumor assessment for crizotinib therapy. Adverse event reporting should follow the 
same guidelines as described in Section 8 of the protocol. Data for patients receiving 
crizotinib following PF-06463922 will be collected in a separate CRF and analyzed 
separately. 
1. Patient Selection 
Inclusion Criteria: 
1. ECOG Performance Status (PS) 0. 1 or 2. 
2. Adequate Bone Marrow, Pancreatic, Renal and Liver function as defined by: 
• Absolute Neutrophil Count (ANC) 1.5 x 109/L; 
• Platelets 100 x 109/L; 
• Hemoglobin 9 g/dL; 
• Serum lipase 1.5 ULN; 
• Serum creatinine 1.5 x ULN or estimated creatinine clearance 60 mL/min as 
calculated using the method standard for the institution; 
• Total serum bilirubin 1.5 x ULN; 
• Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) 2.5 x 
ULN; 5.0 x ULN if there is liver metastases involvement. 
3. Acute effects of any prior therapy resolved to baseline severity or to CTCAE 
Grade 1 except for AEs that in the investigator’ judgment do not constitute a safety 
risk for the patient. 
4. Serum pregnancy test (for females of childbearing potential) negative at screening. A 
patient is of childbearing potential if, in the opinion of the investigator, she is 
biologically capable of having children and is sexually active. 

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5. Evidence of a personally signed and dated informed consent document indicating that 
the patient has been informed of all pertinent aspects of the study (reconseting is not 
necessary if the patient already consented to receiving crizotinib following 
PF-06463922). 
6. Willingness and ability to comply with the study scheduled visits, treatment plans, 
laboratory tests and other procedures. 
7. Male and female patients of childbearing potential and at risk for pregnancy must 
agree to use a highly effective method of contraception from the time of the first 
negative pregnancy test at screening, throughout the study and for 90 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. 
Exclusion Criteria: 
All Section 4.2 Exclusion Criteria apply plus: 
1. Anticancer treatment except palliative radiation therapy between last 
PF-06463922 dose and first crizotinib dose. 
2. Any history of pneumonitis or interstial lung disease. 
2.  Life Style Guidelines for Crizotinib: 
2.1. 
Contraception 
All male subjects who are able to father children and female subjects who are of childbearing 
potential and are sexually active and at risk for pregnancy must agree to use a highly 
effective method of contraception throughout the study and continued for 90 days after the 
last dose. 
The investigator, in consultation with the patient, will select an appropriate method of 
contraception for the individual patient from the permitted list of contraception methods, and 
instruct the patient in their consistent and correct use. The investigator, at each study visit, 
will discuss with the patient the need to use a highly effective contraception consistently and 
correctly and document such conversation in the patient chart. The patient may be contacted 
by phone to confirm contraception is still appropriate per the protocol. In addition, the 
investigator will instruct the patient to call immediately if a selected birth control method is 
discontinued or if pregnancy is known or suspected. 
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: 

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1. Established use of oral, inserted, injected or implanted hormonal methods of 
contraception are allowed provided the patient remains on the same treatment 
throughout the entire study and has been using that hormonal contraceptive for an 
adequate period of time to ensure effectiveness. 
2. Correctly placed copper containing intrauterine device (IUD). 
3. Male condom must be used in association with a female highly effective method of 
contraception. . 
4. Male sterilization with appropriately confirmed absence of sperm in the 
post-vasectomy ejaculate. 
5. Bilateral tubal ligation or bilateral salpingectomy. 
2.2. Sunlight Exposure 
Patients treated with crizotinib should avoid sunbathing, prolonged unprotected sun 
exposure, or tanning for the duration of the study period. 
3.0. 
Concomitant Treatments 
All concomitant treatments, blood products, as well as non drug interventions (eg, 
paracentesis) received by patients from the first dose of crizotinib to 28 days after the last 
dose of study treatment will be recorded on the CRF as detailed in Table 23. Anticancer 
therapy with agents other than crizotinib is not allowed. The metabolism of crizotinib is 
predominantly mediated by the CYP3A isozymes in human liver microsomes and 
hepatocytes. Co-administration with drugs that are CYP3A inhibitors and inducers may 
change the plasma concentrations of crizotinib in humans. The concurrent use of potent 
CYP3A inhibitors, including but not limited to atazanavir, clarithromycin, indinavir, 
itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, telithromycin, troleandomycin, 
saquinavir, voriconazole, and grapefruit or grapefruit juice, are not allowed in the study. The 
topical use of these medications (if applicable), such as 2% ketoconazole cream, may be 
allowed. The concurrent use of potent CYP3A inducers, including but not limited to 
carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, and St. John’s wort, are not 
allowed in the study. 
In vitro data indicate that the most pronounced inhibitory potential of crizotinib was observed 
toward CYP3A4 (testosterone)-mediated drug metabolism. Crizotinib has minimal potential 
to inhibit other human CYP isoforms such as CYP1A2, 2C8, 2C9, 2C19 and 2D6. Crizotinib 
also showed time-dependent inhibition of CYP3A isozymes in human liver microsomes. In 
cancer patients, a mean 3.6-fold (90% CI: 2.7-4.9) increase in the oral midazolam AUC was 
observed following 28 days of crizotinib dosing at 250 mg BID, suggesting that crizotinib is 
a moderate inhibitor of CYP3A. Caution (excluding those restricted medications mentioned 
above) must be exercised in patients receiving crizotinib in combination with drugs that are 
predominantly metabolized by CYP3A such as alfentanil, cyclosporine, fentanyl, quinidine, 
sirolimus, and tacrolimus. In particular, co-administration of crizotinib with 

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CYP3A4 substrates with narrow therapeutic indices including, but not limited to 
dihydroergotamine, ergotamine, pimozide, astemizole*, cisapride*, and terfenadine* 
(*withdrawn from U.S. market) must be avoided from the time of the first dose of crizotinib 
until treatment discontinuation. 
Additionally, the concurrent use of non-prescription drugs, complementary medicines 
(excluding vitamins) or herbal supplements is not recommended. 
3.1. Antiemetic and Antidiarrheal Therapy 
Supportive care may include premedication with antiemetics to limit treatment-related nausea 
and vomiting. Patients may receive prophylaxis of treatment-induced diarrhea. Taking the 
medication with food may reduce nausea. Prophylactic use of antiemetics should be 
considered. 
3.2. Hematopoietic Growth Factors 
The use of hematopoietic growth factors is at the discretion of the treating physician. 
Patients who enter the study on stable doses of erythropoietin or darbepoietin may continue 
this treatment, and patients may start either drug during the study at the discretion of the 
treating physician. However, in Japan, erythropoietin and darbepoietin will not be allowed to 
be used for chemotherapy-related anemia because these drugs have not been approved for 
this indication. Patients with neutropenic fever or infection should be treated promptly and 
may receive therapeutic colony-stimulating factors if appropriate. 
3.3. Other Concomitant Medications 
Anti-inflammatory or narcotic analgesics may be offered as needed. Packed red blood cell 
and platelet transfusions should be administered as clinically indicated. Patients on this trial 
may be supported with appropriate hormone replacement therapy as clinically indicated in 
the absence of disease progression or unacceptable treatment-associated toxicity. 
Bisphosphonate therapy for metastatic bone disease is permitted. Bisphosphonate therapy 
should be given as per local medical practice. Acetaminophen/paracetamol to a maximum 
total daily dose of 2 g is permitted. Daily intake over 2 g is prohibited. Medications that are 
known to prolong the QT interval and bradycardic agents (eg, betablockers, 
non-dihydropyridine calcium channel blockers such as verapamil and diltiazem, clonidine, 
digoxin) should be used with caution during the study. 
3.4. Concomitant Radiotherapy or Surgery 
Palliative radiotherapy to specific sites of disease is permitted if considered medically 
necessary by the treating physician. Crizotinib treatment should be interrupted during 
palliative radiotherapy; stopping 1 day before and resuming treatment 1 day after. 

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The effect of crizotinib in wound healing is not known and has not been investigated; 
therefore, caution is advised on theoretical grounds (potential antiangiogenic effect) for any 
surgical procedures during the study. The appropriate interval of time between surgery and 
crizotinib required to minimize the risk of impaired wound healing and bleeding has not been 
determined. In the event elective surgery is necessary during study participation, crizotinib 
dosing should be stopped 48 hours before surgery and resumed no sooner than 48 hours after 
surgery. Postoperatively, the decision to reinitiate crizotinib treatment should be based on a 
clinical assessment of satisfactory wound healing and recovery from surgery. 
4.  Study Treatment 
Patients will receive a starting dose of crizotinib 250 mg BID which will be administered 
orally at approximately the same time each day on a continuous daily dosing schedule, ie, no 
break in dosing. Crizotinib can be dosed without regard to meals. Cycles are defined as 
21 days in length. 
4.1. Allocation to Treatment 
Patient registration will be same automated registration system as used for PF-06463922. 
4.2. Formulation and Packaging 
Crizotinib will be provided as capsules containing 250 mg and 200 mg of study medication 
and will be packaged in HDPE bottles. Study medication will be supplied by Pfizer. 
4.3. Preparation and Dispensing 
Crizotinib will be supplied as 200 mg and 250 mg capsules for oral administration. 
Crizotinib will be dispensed at the beginning of each treatment cycle (or as otherwise 
indicated). Patients should be instructed to keep their medication in the bottles provided and 
not transfer it to any other container. 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. 
Site personnel must ensure that patients clearly understand the directions for self-medication. 
Patients should be given sufficient supply to last until their next study visit. Patients will be 
provided with Drug Administration Cards and Patient Diaries. In addition, administration 
instructions will be detailed in the Investigational Product (IP) Manual. 
Patients will swallow the study medication whole and will not manipulate or chew the 
medication prior to swallowing. Other administration modalities than what described above 
are not permitted during the study. Patients should be instructed that if they vomit anytime 
after taking a dose, then they must not “make it up” with an extra dose, but instead, resume 
subsequent doses as prescribed. Any missed dose may be taken up to 6 hours prior to the 
next scheduled dose, otherwise it should be skipped and dosing resumed with subsequent 
doses as prescribed. 

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4.4. Compliance 
See Section 5.2.8 of the protocol. Same instructions apply for crizotinib. 
4.5. Drug Storage and Drug Accountability 
Crizotinib should be stored in its original container and in accordance with the drug label. 
See Section 5.2.9 of the protocol for details on drug accountability for crizotinib, as the same 
instructions for PF-06463922 apply for crizotinib. 
4.6. Temperature Excursions 
See Section 5.2.10 of the protocol. Same instructions apply for crizotinib. 
4.7. Dose Modifications for Crizotinib 
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 Table 21 and Table 22. In the event of multiple toxicities, dose modification should be 
based on the worst toxicity observed. Patients are to be instructed to notify their 
investigators at the first occurrence of any adverse event. 
Dose modifications may occur in 3 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. 
Patients will be monitored closely for toxicity and the dose of crizotinib may be adjusted as 
indicated in the dose modification table below (Table 21). 
Table 21. Dose Modifications for Crizotinib 
 
Current Dose Level 
Dose Level -1 
Dose Level -2 
250 mg BID 
200 mg BID 
250 mg QD 
 
Patients requiring more than 2 dose reductions due to treatment-related toxicity will be 
discontinued from the study. 
Investigators are encouraged to employ best supportive care according to local institutional 
clinical practices and according to the guidance for selected adverse events provided below. 

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Table 22. Crizotinib Dose Modifications for Treatment-Related Toxicity 
 
Toxicity 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Non-hematologic General 
(except as noted below), eg, 
neuropathy, edema 
(including peripheral edema 
and localized edema), 
fatigue, and skin rash 
(including erythematous, 
macular, papular, and 
pruritic rash). 
Continue at the 
same dose level. 
Continue at the same 
dose level. 
Withhold dose until toxicity is 
Grade 1, or has returned to 
baseline, then resume treatment at 
the same dose level or reduce the 
dose by 1 level at the discretion of 
the investigator.* 
Withhold dose until 
toxicity is Grade 1, or 
has returned to baseline, 
then reduce the dose by 
1 level and resume 
treatment, or discontinue 
at the discretion of the 
investigator.* 
ALT or AST elevation with 
total bilirubin <2 X ULN 
(in the absence of 
cholestasis or hemolysis).§ 
Continue at the 
same dose level. 
Continue at the same 
dose level. Obtain repeat 
ALT or ALT and total 
bilirubin when 
symptomatic or within 
7 days. 
For France only: 
Consult with Sponsor 
(according to letter 
provided under separate 
cover) to determine 
whether (1) to continue 
with same dose, level; (2) 
withhold dose until 
toxicity is Grade 1 or 
has returned to baseline, 
then resume treatment at 
the same dose level; or 
(3) withhold dose until 
toxicity is Grade 1 or 
has returned to baseline, 
then reduce the dose by 
1 level. 
Withhold dose until toxicity is 
grade ≤1, or has returned to 
baseline, then resume treatment by 
reducing the dose by one dose 
level. If Grade 3 ALT or AST 
elevation recurs reduce further (at 
most by 2 dose levels from initial 
dose level). If recurrence at dose 
level -2, discontinue permanently. 
If Grade 3 ALT or AST elevation 
does not recur after at least 
4 weeks, the dose may be 
escalated by single dose level 
increments up to the initial dose 
level. 
For France only: Discontinue 
treatment and do not retreat. 
See Grade 3. 
For France only: 
Discontinue treatment and 
do not retreat. 

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Toxicity 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
ALT or AST elevation 
concurrent with total 
bilirubin elevation 
2 X ULN (in the absence 
of cholestasis or 
hemolysis). 
Continue at the 
same dose level. 
Obtain repeat 
ALT or AST 
and total 
bilirubin within 
48 hours, then 
repeat every 
48-72 hours 
until ALT/AST 
< grade 1. 
Discontinue treatment 
and do not retreat. 
Discontinue treatment and do not 
retreat. 
Discontinue treatment and 
do not retreat. 
Left ventricular systolic 
dysfunction. 
Continue at the 
same dose level. 
Continue at the same 
dose level. 
Discontinue treatment and do not 
retreat. 
Discontinue treatment and 
do not retreat. 
Prolonged QTc 
Continue at the 
same dose level. 
Assess electrolytes and 
concomitant medications. 
Correct any electrolyte or 
magnesium 
abnormalities. 
Withhold until recovery to 
Grade ≤1, then resume at 200 mg 
twice daily. 
In case of recurrence, withhold 
until recovery to Grade ≤1, then 
resume at 250 mg once daily. 
Permanently discontinue in case 
of further Grade ≥3 recurrence. 
Discontinue treatment and 
do not retreat. 
Pneumonitis (in absence of 
disease progression, 
pulmonary embolism, 
positive cultures or 
radiation effect). 
Discontinue 
treatment and do 
not retreat. 
Discontinue treatment 
and do not retreat. 
Discontinue treatment and do not 
retreat. 
Discontinue treatment and 
do not retreat. 
Bradycardia (heart rate less 
than 60 beats per minute). 
Continue at the 
same dose level. 
Withhold until recovery 
to Grade ≤1 or to heart 
rate ≥60. 
Evaluate concomitant 
medications known to 
cause bradycardia, as 
well as anti-hypertensive 
medications. 
Same as for Grade 2 bradycardia. 
Permanently discontinue 
if no contributing 
concomitant medication is 
identified. 
If contributing 
concomitant medication is 
identified and 
discontinued, or its dose 
is adjusted, resume at 

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Toxicity 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
If contributing 
concomitant medication 
is identified and 
discontinued, or its dose 
is adjusted, resume at 
previous dose upon 
recovery to Grade ≤1 or 
to heart rate ≥60. 
If no contributing 
concomitant medication 
is identified, or if 
contributing concomitant 
medications are not 
discontinued or dose 
modified, resume at 
reduced dose upon 
recovery to Grade ≤1 or 
to heart rate ≥60. 
250 mg once daily upon 
recovery to Grade ≤1 or 
to heart rate ≥60, with 
frequent monitoring. 
Permanently discontinue 
for recurrence. 
Visual disturbance. 
Continue at the 
same dose level. 
Continue at the same 
dose level. 
Interrupt crizotinib until recovery. 
Resume treatment by reducing by 
one dose level. 
Discontinue treatment and 
do not retreat. 
Hematologic (excluding 
lymphopenia**). 
Continue at the 
same dose level. 
Continue at the same 
dose level. 
Withhold dose until toxicity is 
Grade 2, or has returned to 
baseline, then resume treatment at 
the same dose level or reduce by 
1 level after discussion with the 
Sponsor.** 
Withhold dose until 
toxicity is Grade 2, or 
has returned to baseline, 
then reduce the dose by 
1 level and resume 
treatment.** 
* 
Patients who develop Grade 4 hyperuricemia or Grade 3 hypophosphatemia without clinical symptoms may continue study treatment without interruption at 
the discretion of the investigator. Nausea, vomiting, or diarrhea must persist at Grade 3 or 4 despite maximal medical therapy, to require dose modification. 
** Patients who develop Grade 3 or 4 lymphopenia without other dose-limiting events (eg, opportunistic infection) may continue study treatment without 
interruption. 
§ 
Patients entering with ALT and/or AST 5 x ULN (ie, Grade 3) due to underlying malignancy will be monitored for potential drug related increases at 
which point dose modifications will be discussed with the Sponsor (Note: this option does not apply for France). 

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Table 23. Schedule of Assessments for Patients Receiving Crizotinib Following PF-06463922 
 
Protocol Activities 
Within 2 Weeks of 
First Crizotinib 
Dose 
Cycle 1 
Every other Cycle 
End of 
Treatment12 
Follow-up13 
Day 1 
Day 1 of Every other 
Cycle (4 days) 
2 days 
7 days 
Physical Examination 
X 
X 
Blood Pressure and Pulse Rate 
X 
X 
ECOG Performance Status 
X 
X 
Laboratory Studies 
Hematology, Blood Chemistry1 
X 
X 
As per local practice 
Coagulation2 
X 
Urinalysis dipstick and Reflex Microscopy4 
Korea only: X 
(all other countries: as 
clinically indicated) 
X 
Korea only: X 
(all other countries: as 
clinically indicated) 
Korea only: X 
(all other countries: 
as clinically 
indicated) 
12-lead Electrocardiogram3 
X 
Female patients: Pregnancy Test (as 
appropriate)5 
X 
(every cycle 2 days) 
X 
X 
Contraceptive Check (as appropriate)6 
(every cycle 2 days) 
X 
X 
Disease Assessments 
Tumor Assessments/7 
X 
As per local practice 
X 
Other Assessments 
Tumor tissue for molecular profiling8 
X 
X 
Blood Specimens for Circulating Nucleic 
Acid (CNA) Profiling9 
X 
X 
Multiple Gate Acquisition (MUGA) Scan or 
Echocardiogram (France and Japan only) 
France and Japan 
only 
France and Japan 
only: every 4 cycles 
Adverse Events10 
X 
X 
X 
X 
Concomitant Medications/Treatments11 
X 
Survival Follow-up 
X 
Study Treatment 
Crizotinib 
Twice daily 

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Footnotes for Schedule of Activities 
1. 
Hematology: hemoglobin, platelet count, white blood count and differential. Labs may be collected within 72 hours of cycle. 
Chemistry: total bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, total protein, albumin, sodium, potassium, chloride, total 
calcium, phosphorus, blood urea nitrogen (BUN) for EU-only sites, creatinine, uric acid magnesium, glucose, LDH. 
2. 
Coagulation: protime INR. Labs may be collected within 72 hours of cycle. 
3. 
12-Lead ECG: Collect within 2 weeks of last PF-06463922 dose. 
4. 
Reflex Microscopy required if urine dipstick is positive for blood or protein. Dipstick may be collected within 72 hours of cycle. 
5. 
Pregnancy Test: it will be routinely repeated at every cycle (±2 days) during the active treatment period, at the end of study therapy (±- 2 days), at first follow-up visit 
(± 7 days), and additionally whenever one menstrual cycle is missed or when potential pregnancy is otherwise suspected. Additional pregnancy tests may also be undertaken 
if requested by IRB/IECs or if required by local regulations. Patients will provide the laboratory test results carried out at a non-clinical site laboratory, eg, by telephone, and 
bring a copy of the laboratory test results at the next cycle visit. The copy of the laboratory test results must be retained in the patient’s file at the clinical site for 
documentation purposes. 
6. 
Contraceptive check: patient may be contacted by phone to confirm contraception is still appropriate per the protocol. Males and females of childbearing potential must be 
contacted post-study to ensure that they continue to use appropriate contraception for at least 90 days after the last dose of study drug. 
7. 
Tumor Assessments: Patients who are coming off treatment with PF-06463922 will be re-baselined using the last set of tumor assessments performed and will be performed 
using RECIST 1.1. If the last set of tumor assessments is not performed within the past 6 weeks, a new baseline will need to be obtained. Tumor assessments will include all 
known or suspected disease sites. Imaging will include brain (even if brain metastases not suspected) chest, abdomen and pelvis CT or MRI scans. CT scans are 
recommended for assessment of thorax, abdomen and pelvis lesions. Gadolinium contrast enhanced MRI must be used for assessment of CNS lesions with contingent slices of 
1 mm for lesions 5 mm – 10 mm in size, 5 mm for lesions greater than 10 mm. Bone scans (or bone MRI if preferred by investigator) will be performed at baseline for all 
patients and repeated as per local practice. Subsequent tumor assessments will be performed as per local practice. 
8. 
De Novo Tumor Specimens: If feasible and if consent is given, a de novo biopsy will be performed prior to initiating treatment with crizotinib, if not collected at End of 
Treatment with PF-06463922. Pleural effusions (PE) cell pellets may substitute for tumor core biopsy as appropriate. Fine needle aspiration (FNA) samples are not 
acceptable. If local country regulations do not allow for tumor biopsy block to be submitted, 5-micon FFPE tumor slides (at least 12 slides) are acceptable. Samples will be 
sent to a dedicated laboratory as defined by the study sponsor and outlined in the study manual. 
9. 
Blood Specimens for Circulating Nucleic Acid (CNA) Profiling: 10 ml blood specimen optimized for plasma preparation for nucleic acid analysis (eg, circulating free DNA 
(cfDNA) or RNA (cfRNA)) will be collected at screening, and at End of Treatment. Details for handling of these specimens including processing, storage, and shipment will 
be provided in the Study Manual. 
10. Adverse Events: A new Adverse Event log will be used for patients receiving crizotinib following PF-06463922. Patients must be followed for adverse events until at least 
28 days after the last dose of study treatment, or until all serious or study drug-related toxicities have resolved or are determined to be “chronic” or “stable”, whichever is later. 
SAEs will be collected For SAEs, the active reporting period to Pfizer or its designated representative begins from the time that the patient provides informed consent, which is 
obtained prior to the patient’s participation in the study, ie, prior to undergoing any study-related procedure and/or receiving investigational product, through and including 
28 calendar days after the last administration of the investigational product. Serious adverse events occurring to a patient after the active reporting period has ended should be 
reported to the Sponsor if the investigator becomes aware of them; at a minimum, all serious adverse events that the investigator believes have at least a reasonable possibility 
of being related to study drug are to be reported to the Sponsor. 
11. Concomitant Medications/Treatments: Concomitant medications and treatments will be collected at screening. During the treatment, concomitant medications will be 
assessed by investigator, recorded in the patient’s file but not collected in CRF. 
12. End of Treatment Visit: Obtain these assessments if not completed in the last week. 
13. Follow up: At least 28 days, and no more than 35 days after discontinuation of treatment patients will return to undergo assessment for resolution of any treatment-related 
toxicity, and pregnancy test for female patients. 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. After study discontinuation the 
survival follow-up will be performed every 2 months and will include also the collection of information on subsequent anticancer therapies (telephone contact is acceptable). 

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The following table provides a list of examples and should not be considered an all-inclusive 
listing:49 
 

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1. GCP Training 
Prior to enrollment of any subjects, the investigator and any sub-investigators will complete 
the Pfizer-provided Good Clinical Practice training course (“Pfizer GCP Training”) or 
training deemed equivalent by Pfizer. Any investigators who later join the study will 
complete the Pfizer GCP Training or equivalent before performing study-related duties. For 
studies of applicable duration, the investigator and sub-investigators will complete Pfizer 
GCP Training or equivalent every three years during the term of the study, or more often if 
there are significant changes to the ICH GCP guidelines or course materials. 
2. Investigational Product 
No subjects or third-party payers will be charged for investigational product. 
3. Inspections 
The investigator(s) will notify Pfizer or its service provider immediately of any regulatory 
inspection notification in relation to the study. Furthermore, the investigator will cooperate 
with Pfizer or its service provider to prepare the study site for the inspection and will allow 
Pfizer or its service provider (if not prohibited by law) to be present during the inspection. 
The study site and investigator will promptly resolve any discrepancies that are identified 
between the study data and the subject's medical records. The investigator will promptly 
provide copies of the inspection findings to Pfizer or its service provider. Before response 
submission to the regulatory authorities, the investigator will provide Pfizer or its service 
provider with an opportunity to review and comment on responses to any such findings.