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Clinical Trial Results:
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

Summary
EudraCT number	2013-002620-17
Trial protocol	ES DE GB IT BE
Global end of trial date

Results information
Results version number	v1
This version publication date	24 Mar 2018
First version publication date	24 Mar 2018
Other versions	v2

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

B7461001

ISRCTN number

US NCT number

NCT01970865

WHO universal trial number (UTN)

Sponsor organisation name

Pfizer, Inc.

Sponsor organisation address

235 E 42nd Street, New York, United States, NY 10017

Public contact

Pfizer ClinicalTrials.gov Call Center, Pfizer, Inc., +1 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com

Scientific contact

Pfizer ClinicalTrials.gov Call Center, Pfizer, Inc., +1 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Interim

Date of interim/final analysis

22 Nov 2017

Is this the analysis of the primary completion data?

Yes

Primary completion date

15 Mar 2017

Global end of trial reached?

Main objective of the trial

The primary objective of the Phase 1 portion of the study was to assess safety and tolerability of lorlatinib as a single agent at increasing dose levels in subjects with advanced anaplastic lymphoma kinase (ALK) positive or advanced ROS1-positive non-small cell lung cancer (NSCLC) in order to estimate the Maximum Tolerated Dose (MTD) and select the Recommended Phase 2 Dose (RP2D). The primary objective of the Phase 2 portion of the study was to evaluate overall (intra- and extra-cranial) and intra-cranial anti-tumor activity of single-agent lorlatinib at RP2D in subjects with advanced ALK-positive NSCLC and advanced ROS1-positive NSCLC.

Protection of trial subjects

This study was conducted in compliance with the ethical principles originating in or derived from the Declaration of Helsinki and in compliance with all International Council for Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. In addition, all local regulatory requirements were followed, in particular, those affording greater protection to the safety of subjects.

Background therapy

Evidence for comparator

Actual start date of recruitment

08 Jan 2014

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Australia: 23

Country: Number of subjects enrolled

Canada: 7

Country: Number of subjects enrolled

France: 31

Country: Number of subjects enrolled

Germany: 1

Country: Number of subjects enrolled

Hong Kong: 2

Country: Number of subjects enrolled

Italy: 27

Country: Number of subjects enrolled

Japan: 42

Country: Number of subjects enrolled

Korea, Republic of: 4

Country: Number of subjects enrolled

Singapore: 26

Country: Number of subjects enrolled

Spain: 30

Country: Number of subjects enrolled

Switzerland: 7

Country: Number of subjects enrolled

Taiwan: 11

Country: Number of subjects enrolled

United States: 121

Worldwide total number of subjects

332

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

270

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

A total of 334 subjects were enrolled in this study, and 2 of them (one each in Phase 1 and Phase 2) didn't receive any study treatment.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

10 mg QD (Phase 1)

Arm description

PF-06463922 10 mg was orally given once daily (QD) on Day -7 and in 21-day cycles from Cycle 1 Day 1 until progression of disease (unless clinical benefit was still achievable), unacceptable toxicity, death or consent withdrawal.

Arm type

Experimental

Investigational medicinal product name

PF-06463922

Investigational medicinal product code

Other name

Lorlatinib

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

PF-06463922 10 mg was administered QD with at least 240 mL of water on an empty stomach. No food or liquids other than water were consumed for 2 hours before and 2 hours following each dose.

25 mg QD (Phase 1)

Arm description

PF-06463922 25 mg was orally given once daily (QD) in 21-day cycles from Cycle 1 Day 1 until progression of disease (unless clinical benefit was still achievable), unacceptable toxicity, death or consent withdrawal. Midazolam 2 mg was orally given QD on Day -7 and Cycle 1 Day 15.

Arm type

Experimental

Investigational medicinal product name

Midazolam

Investigational medicinal product code

Other name

Pharmaceutical forms

Syrup

Routes of administration

Oral use

Dosage and administration details

Midazolam 2 mg was administered alone on Day -7 and concurrently with PF-06463922 on Cycle 1 Day 15.

Investigational medicinal product name

PF-06463922

Investigational medicinal product code

Other name

Lorlatinib

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

PF-06463922 25 mg was administered QD with at least 240 mL of water on an empty stomach. No food or liquids other than water were consumed for 2 hours before and 2 hours following each dose.

50 mg QD (Phase 1)

Arm description

PF-06463922 50 mg was orally given once daily (QD) on Day -7 and in 21-day cycles from Cycle 1 Day 1 until progression of disease (unless clinical benefit was still achievable), unacceptable toxicity, death or consent withdrawal.

Arm type

Experimental

Investigational medicinal product name

PF-06463922

Investigational medicinal product code

Other name

Lorlatinib

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

PF-06463922 50 mg was administered QD with at least 240 mL of water on an empty stomach. No food or liquids other than water were consumed for 2 hours before and 2 hours following each dose.

75 mg QD (Phase 1)

Arm description

PF-06463922 75 mg was orally given once daily (QD) on Day -7 and in 21-day cycles from Cycle 1 Day 1 until progression of disease (unless clinical benefit was still achievable), unacceptable toxicity, death or consent withdrawal.

Arm type

Experimental

Investigational medicinal product name

PF-06463922

Investigational medicinal product code

Other name

Lorlatinib

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

PF-06463922 75 mg was administered QD with at least 240 mL of water on an empty stomach. No food or liquids other than water were consumed for 2 hours before and 2 hours following each dose.

100 mg QD (Phase 1)

Arm description

PF-06463922 100 mg was orally given once daily (QD) on Day -7 and in 21-day cycles from Cycle 1 Day 1 until progression of disease (unless clinical benefit was still achievable), unacceptable toxicity, death or consent withdrawal.

Arm type

Experimental

Investigational medicinal product name

PF-06463922

Investigational medicinal product code

Other name

Lorlatinib

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

PF-06463922 100 mg was administered QD with at least 240 mL of water on an empty stomach. No food or liquids other than water were consumed for 2 hours before and 2 hours following each dose.

150 mg QD (Phase 1)

Arm description

PF-06463922 150 mg was orally given once daily (QD) in 21-day cycles from Cycle 1 Day 1 until progression of disease (unless clinical benefit was still achievable), unacceptable toxicity, death or consent withdrawal. Midazolam 2 mg was orally given QD on Day -7 and Cycle 1 Day 15.

Arm type

Experimental

Investigational medicinal product name

Midazolam

Investigational medicinal product code

Other name

Pharmaceutical forms

Syrup

Routes of administration

Oral use

Dosage and administration details

Midazolam 2 mg was administered alone on Day -7 and concurrently with PF-06463922 on Cycle 1 Day 15.

Investigational medicinal product name

PF-06463922

Investigational medicinal product code

Other name

Lorlatinib

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

PF-06463922 150 mg was administered QD with at least 240 mL of water on an empty stomach. No food or liquids other than water were consumed for 2 hours before and 2 hours following each dose.

200 mg QD (Phase 1)

Arm description

PF-06463922 200 mg was orally given once daily (QD) on Day -7 and in 21-day cycles from Cycle 1 Day 1 until progression of disease (unless clinical benefit was still achievable), unacceptable toxicity, death or consent withdrawal.

Arm type

Experimental

Investigational medicinal product name

PF-06463922

Investigational medicinal product code

Other name

Lorlatinib

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

PF-06463922 200 mg was administered QD with at least 240 mL of water on an empty stomach. No food or liquids other than water were consumed for 2 hours before and 2 hours following each dose.

35 mg BID (Phase 1)

Arm description

PF-06463922 35 mg was orally given twice daily (BID) on Day -7 and in 21-day cycles from Cycle 1 Day 1 until progression of disease (unless clinical benefit was still achievable), unacceptable toxicity, death or consent withdrawal.

Arm type

Experimental

Investigational medicinal product name

PF-06463922

Investigational medicinal product code

Other name

Lorlatinib

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

PF-06463922 35 mg was administered BID with at least 240 mL of water on an empty stomach. No food or liquids other than water were consumed for 2 hours before and 2 hours following each dose.

75 mg BID (Phase 1)

Arm description

PF-06463922 75 mg was orally given twice daily (BID) on Day -7 and in 21-day cycles from Cycle 1 Day 1 until progression of disease (unless clinical benefit was still achievable), unacceptable toxicity, death or consent withdrawal.

Arm type

Experimental

Investigational medicinal product name

PF-06463922

Investigational medicinal product code

Other name

Lorlatinib

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

PF-06463922 75 mg was administered BID with at least 240 mL of water on an empty stomach. No food or liquids other than water were consumed for 2 hours before and 2 hours following each dose.

100 mg BID (Phase 1)

Arm description

PF-06463922 100 mg was orally given twice daily (BID) on Day -7 and in 21-day cycles from Cycle 1 Day 1 until progression of disease (unless clinical benefit was still achievable), unacceptable toxicity, death or consent withdrawal.

Arm type

Experimental

Investigational medicinal product name

PF-06463922

Investigational medicinal product code

Other name

Lorlatinib

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

PF-06463922 100 mg was administered BID with at least 240 mL of water on an empty stomach. No food or liquids other than water were consumed for 2 hours before and 2 hours following each dose.

EXP-1 (Phase 2)

Arm description

Treatment-naïve subjects with advanced ALK-positive NSCLC with or without asymptomatic central nervous system (CNS) metastases were given PF-06463922 100 mg orally once daily (QD) on Day -7 (only for subjects scheduled for pharmacokinetic evaluation) and in 21-day cycles from Cycle 1 Day 1 until progression of disease (unless clinical benefit was still achievable), unacceptable toxicity, death or consent withdrawal.

Arm type

Experimental

Investigational medicinal product name

PF-06463922

Investigational medicinal product code

Other name

Lorlatinib

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

PF-06463922 100 mg was administered QD with at least 240 mL of water on an empty stomach. No food or liquids other than water were consumed for 2 hours before and 2 hours following each dose.

EXP-2 (Phase 2)

Arm description

Subjects with advanced ALK-positive NSCLC with or without asymptomatic CNS metastases relapsing after only crizotinib therapy were given PF-06463922 100 mg orally once daily (QD) on Day -7 (only for subjects scheduled for pharmacokinetic evaluation) and in 21-day cycles from Cycle 1 Day 1 until progression of disease (unless clinical benefit was still achievable), unacceptable toxicity, death or consent withdrawal.

Arm type

Experimental

Investigational medicinal product name

PF-06463922

Investigational medicinal product code

Other name

Lorlatinib

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

PF-06463922 100 mg was administered QD with at least 240 mL of water on an empty stomach. No food or liquids other than water were consumed for 2 hours before and 2 hours following each dose.

EXP-3 (Phase 2)

Arm description

Subjects with advanced ALK-positive 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, or subjects with advanced ALK-positive 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 were given PF-06463922 100 mg orally once daily (QD) on Day -7 (only for subjects scheduled for pharmacokinetic evaluation) and in 21-day cycles from Cycle 1 Day 1 until progression of disease (unless clinical benefit was still achievable), unacceptable toxicity, death or consent withdrawal.

Arm type

Experimental

Investigational medicinal product name

PF-06463922

Investigational medicinal product code

Other name

Lorlatinib

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

PF-06463922 100 mg was administered QD with at least 240 mL of water on an empty stomach. No food or liquids other than water were consumed for 2 hours before and 2 hours following each dose.

EXP-4 (Phase 2)

Arm description

subjects with advanced ALK-positive NSCLC with or without asymptomatic CNS metastases relapsing after 2 prior lines of ALK inhibitor therapies were given PF-06463922 100 mg orally once daily (QD) on Day -7 (only for subjects scheduled for pharmacokinetic evaluation) and in 21-day cycles from Cycle 1 Day 1 until progression of disease (unless clinical benefit was still achievable), unacceptable toxicity, death or consent withdrawal.

Arm type

Experimental

Investigational medicinal product name

PF-06463922

Investigational medicinal product code

Other name

Lorlatinib

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

PF-06463922 100 mg was administered QD with at least 240 mL of water on an empty stomach. No food or liquids other than water were consumed for 2 hours before and 2 hours following each dose.

EXP-5 (Phase 2)

Arm description

Subjects with advanced ALK-positive NSCLC with or without asymptomatic CNS metastases relapsing after 3 prior lines of ALK inhibitor therapies were given PF-06463922 100 mg orally once daily (QD) on Day -7 (only for subjects scheduled for pharmacokinetic evaluation) and in 21-day cycles from Cycle 1 Day 1 until progression of disease (unless clinical benefit was still achievable), unacceptable toxicity, death or consent withdrawal.

Arm type

Experimental

Investigational medicinal product name

PF-06463922

Investigational medicinal product code

Other name

Lorlatinib

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

PF-06463922 100 mg was administered QD with at least 240 mL of water on an empty stomach. No food or liquids other than water were consumed for 2 hours before and 2 hours following each dose.

EXP-6 (Phase 2)

Arm description

Subjects with advanced ROS1-positive NSCLC who were treatment naïve or had any number of prior cancer therapies with or without asymptomatic CNS metastases were given PF-06463922 100 mg orally once daily (QD) on Day -7 (only for subjects scheduled for pharmacokinetic evaluation) and in 21-day cycles from Cycle 1 Day 1 until progression of disease (unless clinical benefit was still achievable), unacceptable toxicity, death or consent withdrawal.

Arm type

Experimental

Investigational medicinal product name

PF-06463922

Investigational medicinal product code

Other name

Lorlatinib

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

PF-06463922 100 mg was administered QD with at least 240 mL of water on an empty stomach. No food or liquids other than water were consumed for 2 hours before and 2 hours following each dose.

Japan Lead-In Cohort (LIC)

Arm description

Few Japanese subjects were given PF-06463922 100 mg orally once daily (QD) in 21-day cycles from Cycle 1 Day 1 until progression of disease (unless clinical benefit was still achievable), unacceptable toxicity, death or consent withdrawal to evaluate safety of PF-06463922 in Japanese subjects, in order to support inclusion of Japanese subjects in Phase 2.

Arm type

Experimental

Investigational medicinal product name

PF-06463922

Investigational medicinal product code

Other name

Lorlatinib

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

PF-06463922 100 mg was administered QD with at least 240 mL of water on an empty stomach. No food or liquids other than water were consumed for 2 hours before and 2 hours following each dose.

Number of subjects in period 1	10 mg QD (Phase 1)	25 mg QD (Phase 1)	50 mg QD (Phase 1)	75 mg QD (Phase 1)	100 mg QD (Phase 1)	150 mg QD (Phase 1)	200 mg QD (Phase 1)	35 mg BID (Phase 1)	75 mg BID (Phase 1)	100 mg BID (Phase 1)	EXP-1 (Phase 2)	EXP-2 (Phase 2)	EXP-3 (Phase 2)	EXP-4 (Phase 2)	EXP-5 (Phase 2)	EXP-6 (Phase 2)	Japan Lead-In Cohort (LIC)
Started	3	3	3	12	17	3	3	3	3	4	30	27	60	65	46	47	3
Received treatment	3	3	3	12	17	3	3	3	3	4	30	27	60	65	46	47	3
Completed	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Not completed	3	3	3	12	17	3	3	3	3	4	30	27	60	65	46	47	3
Adverse event, serious fatal	3	1	3	4	6	3	1	3	2	1	1	4	14	19	15	10	1
Study ongoing	-	2	-	6	8	-	2	-	1	3	29	22	43	41	29	29	2
Consent withdrawn by subject	-	-	-	1	2	-	-	-	-	-	-	1	2	5	2	7	-
Unspecified	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	1	-
Lost to follow-up	-	-	-	1	1	-	-	-	-	-	-	-	1	-	-	-	-

Baseline characteristics

Top of page

Reporting group title

10 mg QD (Phase 1)

Reporting group description

Reporting group title

25 mg QD (Phase 1)

Reporting group description

Reporting group title

50 mg QD (Phase 1)

Reporting group description

Reporting group title

75 mg QD (Phase 1)

Reporting group description

Reporting group title

100 mg QD (Phase 1)

Reporting group description

Reporting group title

150 mg QD (Phase 1)

Reporting group description

Reporting group title

200 mg QD (Phase 1)

Reporting group description

Reporting group title

35 mg BID (Phase 1)

Reporting group description

Reporting group title

75 mg BID (Phase 1)

Reporting group description

Reporting group title

100 mg BID (Phase 1)

Reporting group description

Reporting group title

EXP-1 (Phase 2)

Reporting group description

Reporting group title

EXP-2 (Phase 2)

Reporting group description

Reporting group title

EXP-3 (Phase 2)

Reporting group description

Reporting group title

EXP-4 (Phase 2)

Reporting group description

Reporting group title

EXP-5 (Phase 2)

Reporting group description

Reporting group title

EXP-6 (Phase 2)

Reporting group description

Reporting group title

Japan Lead-In Cohort (LIC)

Reporting group description

Reporting group values	10 mg QD (Phase 1)	25 mg QD (Phase 1)	50 mg QD (Phase 1)	75 mg QD (Phase 1)	100 mg QD (Phase 1)	150 mg QD (Phase 1)	200 mg QD (Phase 1)	35 mg BID (Phase 1)	75 mg BID (Phase 1)	100 mg BID (Phase 1)	EXP-1 (Phase 2)	EXP-2 (Phase 2)	EXP-3 (Phase 2)	EXP-4 (Phase 2)	EXP-5 (Phase 2)	EXP-6 (Phase 2)	Japan Lead-In Cohort (LIC)	Total
Number of subjects	3	3	3	12	17	3	3	3	3	4	30	27	60	65	46	47	3	332
Age categorical
Units: Subjects
In utero	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Newborns (0-27 days)	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Children (2-11 years)	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Adolescents (12-17 years)	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Adults (18-64 years)	1	2	3	11	16	2	3	2	2	3	22	18	48	56	39	39	3	270
From 65-84 years	2	1	0	1	1	1	0	1	1	1	8	8	12	9	7	8	0	61
85 years and over	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	1
Age Continuous
Units: years
arithmetic mean (standard deviation)	67.3 ± 11.2	53.7 ± 13.0	52.7 ± 10.0	48.2 ± 13.2	49 ± 11.1	55.3 ± 14.7	44.7 ± 4.2	61.3 ± 15.4	61.3 ± 18.1	50.8 ± 15.2	57.4 ± 12.1	57.1 ± 12.7	54 ± 11.9	52.2 ± 11.8	51.5 ± 11.2	52.8 ± 12.9	44.3 ± 6.1	-
Sex: Female, Male
Units: Subjects
FEMALE	2	0	1	7	11	2	2	2	3	2	13	17	38	37	25	27	2	191
MALE	1	3	2	5	6	1	1	1	0	2	17	10	22	28	21	20	1	141
Race/Ethnicity, Customized
Units: Subjects
White\|	2	2	3	7	13	2	2	1	2	3	10	13	25	32	27	25	0	169
Black\|	1	0	0	0	0	1	0	1	0	0	1	0	1	0	0	1	0	6
Asian\|	0	1	0	3	2	0	1	0	0	0	17	10	23	23	14	16	3	113
Other\|	0	0	0	0	1	0	0	0	0	0	1	2	1	3	2	3	0	13
Unspecified\|	0	0	0	2	1	0	0	1	1	1	1	2	10	7	3	2	0	31

Subject analysis set title

ALK Positive Population (Phase 1)

Subject analysis set type

Sub-group analysis

Subject analysis set description

This reporting arm includes all Phase 1 intent-to-treat (ITT) subjects who had documented ALK rearrangement.

Subject analysis set title

ROS1 Positive Population (Phase 1)

Subject analysis set type

Sub-group analysis

Subject analysis set description

This reporting arm includes all Phase 1 intent-to-treat (ITT) subjects who had documented ROS1 rearrangement.

Subject analysis set title

Phase 1 ITT Population

Subject analysis set type

Sub-group analysis

Subject analysis set description

This reporting group includes all Phase 1 intent-to-treat (ITT) subjects.

Subject analysis set title

Phase 1 PRO Evaluable Population

Subject analysis set type

Sub-group analysis

Subject analysis set description

This reporting group includes all Phase 1 subjects who received at least 1 dose of PF-06463922 and completed a baseline and at least 1 post-baseline patient reported outcome (PRO) assessment.

Subject analysis set title

Phase 2 ITT Population

Subject analysis set type

Sub-group analysis

Subject analysis set description

This reporting group includes all Phase 2 intent-to-treat (ITT) subjects.

Subject analysis set title

Phase 2 and Japan LIC PK Analysis Set

Subject analysis set type

Sub-group analysis

Subject analysis set description

PK parameters of PF-06463922 were determined for a small subset of Phase 2 subjects and Japan LIC. These subjects received PF-06463922 100 mg orally QD and were combined into 1 reporting group for PK analysis. Japan LIC was not included in single-dose PK analysis, ie, they did not contribute to Day -7 data.

Subject analysis sets values	ALK Positive Population (Phase 1)	ROS1 Positive Population (Phase 1)	Phase 1 ITT Population	Phase 1 PRO Evaluable Population	Phase 2 ITT Population	Phase 2 and Japan LIC PK Analysis Set
Number of subjects	41	12	53	43	274	22
Age categorical
Units: Subjects
In utero	0	0	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0	0	0
Newborns (0-27 days)	0	0	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0	0	0
Children (2-11 years)	0	0	0	0	0	0
Adolescents (12-17 years)	0	0	0	0	0	0
Adults (18-64 years)	36	8	44	36	221	21
From 65-84 years	5	4	9	7	52	1
85 years and over	0	0	0	0	1	0
Age Continuous
Units: years
arithmetic mean (standard deviation)	51.0 ± 11.2	55.0 ± 18.0	51.9 ± 13.0	51.4 ± 13.2	53.6 ± 12.1	50.9 ± 9.8
Sex: Female, Male
Units: Subjects
FEMALE	24	7	31	24	157	13
MALE	17	5	22	19	117	9
Race/Ethnicity, Customized
Units: Subjects
White\|	32	5	37	31	132	9
Black\|	2	1	3	1	3	0
Asian\|	5	2	7	5	103	11
Other\|	0	1	1	1	11	2
Unspecified\|	2	3	5	5	25	0

End points

Top of page

Reporting group title

10 mg QD (Phase 1)

Reporting group description

Reporting group title

25 mg QD (Phase 1)

Reporting group description

Reporting group title

50 mg QD (Phase 1)

Reporting group description

Reporting group title

75 mg QD (Phase 1)

Reporting group description

Reporting group title

100 mg QD (Phase 1)

Reporting group description

Reporting group title

150 mg QD (Phase 1)

Reporting group description

Reporting group title

200 mg QD (Phase 1)

Reporting group description

Reporting group title

35 mg BID (Phase 1)

Reporting group description

Reporting group title

75 mg BID (Phase 1)

Reporting group description

Reporting group title

100 mg BID (Phase 1)

Reporting group description

Reporting group title

EXP-1 (Phase 2)

Reporting group description

Reporting group title

EXP-2 (Phase 2)

Reporting group description

Reporting group title

EXP-3 (Phase 2)

Reporting group description

Reporting group title

EXP-4 (Phase 2)

Reporting group description

Reporting group title

EXP-5 (Phase 2)

Reporting group description

Reporting group title

EXP-6 (Phase 2)

Reporting group description

Reporting group title

Japan Lead-In Cohort (LIC)

Reporting group description

Subject analysis set title

ALK Positive Population (Phase 1)

Subject analysis set type

Sub-group analysis

Subject analysis set description

This reporting arm includes all Phase 1 intent-to-treat (ITT) subjects who had documented ALK rearrangement.

Subject analysis set title

ROS1 Positive Population (Phase 1)

Subject analysis set type

Sub-group analysis

Subject analysis set description

This reporting arm includes all Phase 1 intent-to-treat (ITT) subjects who had documented ROS1 rearrangement.

Subject analysis set title

Phase 1 ITT Population

Subject analysis set type

Sub-group analysis

Subject analysis set description

This reporting group includes all Phase 1 intent-to-treat (ITT) subjects.

Subject analysis set title

Phase 1 PRO Evaluable Population

Subject analysis set type

Sub-group analysis

Subject analysis set description

This reporting group includes all Phase 1 subjects who received at least 1 dose of PF-06463922 and completed a baseline and at least 1 post-baseline patient reported outcome (PRO) assessment.

Subject analysis set title

Phase 2 ITT Population

Subject analysis set type

Sub-group analysis

Subject analysis set description

This reporting group includes all Phase 2 intent-to-treat (ITT) subjects.

Subject analysis set title

Phase 2 and Japan LIC PK Analysis Set

Subject analysis set type

Sub-group analysis

Subject analysis set description

Primary: Number of Subjects with Cycle 1 Dose-Limiting Toxicities (DLTs) in Phase 1

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End point title

Number of Subjects with Cycle 1 Dose-Limiting Toxicities (DLTs) in Phase 1 ^[1] ^[2]

End point description

DLT was defined as any of the following adverse events (AEs) attributable to PF-06463922: (1) hematologic: grade 4 neutropenia for >7 days; febrile neutropenia; grade >=3 neutropenic infection; grade >=3 thrombocytopenia with bleeding; grade 4 thrombocytopenia; (2) non-hematologic: grade >=3 pancreatitis; grade >=3 toxicities (excluding grade >=3 laboratory abnormalities not requiring dose modifications) persisting after optimal treatment with standard medical therapy; symptomatic grade >=3 QTc prolongation, or asymptomatic grade >=3 prolongation that had been confirmed by repeat testing and re-evaluation by a qualified person, and persisted after correction of reversible causes; >=20% decrease from baseline in left ventricular ejection fraction (LVEF); (3) other: failure to deliver at least 16 out of the 21 prescribed daily total doses due to toxicities attributable to study drug; failure to restart dosing after 21 days (1 cycle) delay due to toxicities attributable to study drug.

End point type

Primary

End point timeframe

Cycle 1 (21 days)

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses were planned for this primary end point.
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: All other reporting arms are not applicable to this end point.

End point values	10 mg QD (Phase 1)	25 mg QD (Phase 1)	50 mg QD (Phase 1)	75 mg QD (Phase 1)	100 mg QD (Phase 1)	150 mg QD (Phase 1)	200 mg QD (Phase 1)	35 mg BID (Phase 1)	75 mg BID (Phase 1)	100 mg BID (Phase 1)
Number of subjects analysed	3	3	3	11	16	3	3	2	3	3
Units: subjects
With DLT\|	0	0	0	0	0	0	1	0	0	0
No DLT\|	3	2	3	6	8	2	1	2	3	2
Data missing\|	0	1	0	5	8	1	1	0	0	1

No statistical analyses for this end point

Primary: Percentage of Subjects with Overall and Intracranial Objective Response (Phase 2)

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End point title

Percentage of Subjects with Overall and Intracranial Objective Response (Phase 2) ^[3] ^[4]

End point description

Objective response (OR) refers to confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1. Intracranial OR refers to confirmed CR or PR considering only lesions within brain. Results presented here were based on independent central review. The intent-to-treat (ITT) analysis set was used for overall response assessment, and included all enrolled subjects with documented ALK or ROS1 rearrangement who received at least 1 dose of PF-06463922; subjects with central nervous system (CNS) metastases in the ITT analysis set were used for intracranial response assessment.

End point type

Primary

End point timeframe

3 years

Notes
[3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses were planned for this primary end point.
[4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: All other reporting arms are not applicable to this end point.

End point values	EXP-1 (Phase 2)	EXP-2 (Phase 2)	EXP-3 (Phase 2)	EXP-4 (Phase 2)	EXP-5 (Phase 2)	EXP-6 (Phase 2)
Number of subjects analysed	30 ^[5]	27 ^[6]	59 ^[7]	65 ^[8]	46 ^[9]	47 ^[10]
Units: percentage of subjects
number (confidence interval 95%)
Objective response\|	90.0 (73.5 to 97.9)	74.1 (53.7 to 88.9)	50.8 (37.5 to 64.1)	41.5 (29.4 to 54.4)	34.8 (21.4 to 50.2)	36.2 (22.7 to 51.5)
Intracranial objective response\|	75.0 (34.9 to 96.8)	58.8 (32.9 to 81.6)	62.5 (43.7 to 78.9)	55.6 (40.0 to 70.4)	39.5 (24.0 to 56.6)	56.0 (34.9 to 75.6)

Notes
[5] - Number of subjects analyzed for intracranial objective response is 8.
[6] - Number of subjects analyzed for intracranial objective response is 17.
[7] - Number of subjects analyzed for intracranial objective response is 32.
[8] - Number of subjects analyzed for intracranial objective response is 45.
[9] - Number of subjects analyzed for intracranial objective response is 38.
[10] - Number of subjects analyzed for intracranial objective response is 25.

No statistical analyses for this end point

Secondary: Percentage of Subjects with Overall and Intracranial Objective Response (Phase 1)

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End point title

Percentage of Subjects with Overall and Intracranial Objective Response (Phase 1)

End point description

Objective response (OR) refers to confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1. Intracranial OR refers to confirmed CR or PR considering only lesions within brain. Results presented here were based on independent central review. The intent-to-treat (ITT) analysis set was used for overall response assessment, and included all enrolled subjects with documented ALK or ROS1 rearrangement who received at least 1 dose of PF-06463922; subjects with CNS metastases in the ITT analysis set was used for intracranial response assessment.

End point type

Secondary

End point timeframe

3 years

End point values	ALK Positive Population (Phase 1)	ROS1 Positive Population (Phase 1)
Number of subjects analysed	41 ^[11]	12 ^[12]
Units: percentage of subjects
number (confidence interval 95%)
Objective response\|	39.0 (24.2 to 55.5)	50.0 (21.1 to 78.9)
Intracranial objective response\|	41.2 (24.6 to 59.3)	50.0 (15.7 to 84.3)

Notes
[11] - Number of subjects analyzed for intracranial objective response is 34.
[12] - Number of subjects analyzed for intracranial objective response is 8.

No statistical analyses for this end point

Secondary: Time to Tumor Response (TTR) and Intracranial TTR (Phase 1)

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End point title

Time to Tumor Response (TTR) and Intracranial TTR (Phase 1)

End point description

Time to tumor response (TTR) was defined as the time from the first dose of study treatment to the first documentation of objective tumor response (CR or PR). For subjects whose objective response proceeded from PR to CR, the onset of PR was taken as the onset of response. TTR was only calculated for the subgroup of subjects with a confirmed objective tumor response. Intracranial TTR was only calculated for subjects with confirmed intracranial objective response. Results presented here were based on independent central review.

End point type

Secondary

End point timeframe

3 years

End point values	ALK Positive Population (Phase 1)	ROS1 Positive Population (Phase 1)
Number of subjects analysed	16 ^[13]	6 ^[14]
Units: months
median (full range (min-max))
TTR\|	1.4 (1.2 to 15.2)	1.4 (1.2 to 2.8)
Intracranial TTR\|	1.4 (1.2 to 20.1)	1.4 (1.1 to 2.8)

Notes
[13] - Number of subjects analyzed for intracranial TTR is 14.
[14] - Number of subjects analyzed for intracranial TTR is 4.

No statistical analyses for this end point

Secondary: Duration of Response (DOR) and Intracranial DOR (Phase 1)

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End point title

Duration of Response (DOR) and Intracranial DOR (Phase 1)

End point description

Duration of Response (DOR) was 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 occurred first. DOR was only calculated for the subgroup of subjects with a confirmed objective tumor response. Intracranial DOR was only calculated for subjects with confirmed intracranial objective response. Results presented here were based on independent central review. "99999" represents "not applicable" or "non evaluable" data.

End point type

Secondary

End point timeframe

3 years

End point values	ALK Positive Population (Phase 1)	ROS1 Positive Population (Phase 1)
Number of subjects analysed	16 ^[15]	6 ^[16]
Units: months
median (confidence interval 95%)
DOR\|	14.06 (4.17 to 99999)	99999 (9.69 to 99999)
Intra-cranial DOR\|	99999 (14.06 to 99999)	99999 (99999 to 99999)

Notes
[15] - Number of subjects analyzed for intracranial DOR is 14.
[16] - Number of subjects analyzed for intracranial DOR is 4.

No statistical analyses for this end point

Secondary: Percentage of Subjects Achieving Disease Control and Intracranial Disease Control at 12 Weeks (Phase 1)

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End point title

Percentage of Subjects Achieving Disease Control and Intracranial Disease Control at 12 Weeks (Phase 1)

End point description

Tumor response was evaluated according to RECIST version 1.1, and disease control was defined as confirmed complete response (CR), confirmed partial response (PR), or stable disease (SD). Results presented here were based on independent central review. The intent-to-treat (ITT) analysis set was used for overall response assessment, and included all enrolled subjects with documented ALK or ROS1 rearrangement who received at least 1 dose of PF-06463922; subjects with CNS metastases in the ITT analysis set was used for intracranial response assessment.

End point type

Secondary

End point timeframe

12 weeks

End point values	ALK Positive Population (Phase 1)	ROS1 Positive Population (Phase 1)
Number of subjects analysed	41 ^[17]	12 ^[18]
Units: percentage of subjects
number (confidence interval 95%)
Disease control rate\|	53.7 (37.4 to 69.3)	58.3 (27.7 to 84.8)
Intra-cranial disease control rate\|	50.0 (32.4 to 67.6)	37.5 (8.5 to 75.5)

Notes
[17] - Number of subjects analyzed for intracranial disease control rate is 34.
[18] - Number of subjects analyzed for intracranial disease control rate is 8.

No statistical analyses for this end point

Secondary: Probability of First Event Being a Central Nervous System (CNS) Progression, Non CNS Progression, or Death (Phase 1)

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End point title

Probability of First Event Being a Central Nervous System (CNS) Progression, Non CNS Progression, or Death (Phase 1)

End point description

The probability of the first event being a CNS progression, a non-CNS progression, or death was evaluated with a competing risk approach by estimating cumulative incidence functions (range: 0-1) relative to the analysis set. The time to first event being a Competing Event (either “CNS progression” or “non CNS progression” or “Death”) was defined as time from first dose until the date of that specific event. Subjects not known to have any of the Competing Events were censored on the date they were last assessed for disease status for PFS. Subjects who presented one type of event were counted as a competing cause of failure for the analysis of other type of events. For each type of event, the cumulative incidence function corresponding to the nearest time point preceding 1 year is presented. The results are based on independent central review.

End point type

Secondary

End point timeframe

3 years

End point values	Phase 1 ITT Population
Number of subjects analysed	53
Units: not applicable
number (not applicable)
CNS progression	0.260
Non CNS progression	0.352
Death	0.060

No statistical analyses for this end point

Secondary: Progression-Free Survival (PFS) (Phase 1)

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End point title

Progression-Free Survival (PFS) (Phase 1)

End point description

PFS was defined as the time from the first dose of study treatment to the first documentation of objective disease progression or to death on study due to any cause, whichever came first. Results presented here were based on independent central review. PFS analysis set included all subjects with documented ALK or ROS1 rearrangement who received at least 1 dose of PF-06463922. "99999" represents "not applicable" or "non evaluable" data.

End point type

Secondary

End point timeframe

3 years

End point values	ALK Positive Population (Phase 1)	ROS1 Positive Population (Phase 1)
Number of subjects analysed	41 ^[19]	12 ^[20]
Units: months
median (confidence interval 95%)	5.3 (2.5 to 11.8)	10.1 (1.6 to 99999)

Notes
[19] - Number of subjects with objective progression or death is 29; others were censored.
[20] - Number of subjects with objective progression or death is 7; others were censored.

No statistical analyses for this end point

Secondary: Overall Survival (OS) (Phase 1)

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End point title

Overall Survival (OS) (Phase 1)

End point description

OS was defined as the time from first dose to the date of death due to any cause. For subjects still alive at the time of analysis, the OS time was censored on the last date the subjects were known to be alive. Estimates of OS and its 95% confidence interval were determined using Kaplan-Meier method. ITT population was used for OS analysis, and it included all enrolled subjects with documented ALK or ROS1 rearrangement who received at least 1 dose of PF-06463922. "99999" represents "not applicable" or "non evaluable" data.

End point type

Secondary

End point timeframe

3 years

End point values	ALK Positive Population (Phase 1)	ROS1 Positive Population (Phase 1)
Number of subjects analysed	41 ^[21]	12 ^[22]
Units: months
median (confidence interval 95%)	22.3 (11.4 to 99999)	99999 (4.7 to 99999)

Notes
[21] - Number of deaths is 21; others were censored.
[22] - Number of deaths is 5; others were censored.

No statistical analyses for this end point

Secondary: Maximum Observed Plasma Concentration (Cmax) of PF-06463922 Following Single Oral Doses (Phase 1)

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End point title

Maximum Observed Plasma Concentration (Cmax) of PF-06463922 Following Single Oral Doses (Phase 1) ^[23]

End point description

Maximum observed plasma concentration (Cmax) of PF-06463922 was observed directly from data. PK concentration analysis set for PF-06463922 included all subjects treated who had at least 1 concentration of PF-06463922. "99999" represents "not applicable" or "non evaluable" data.

End point type

Secondary

End point timeframe

Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post-dose on Cylce 1 Day 1 for 25 mg QD and 150 mg QD groups; pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24, 48, 72, 96 and 120 hours post-dose on Day -7 for all other groups.

Notes
[23] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: All other reporting arms are not applicable to this end point.

End point values	10 mg QD (Phase 1)	25 mg QD (Phase 1)	50 mg QD (Phase 1)	75 mg QD (Phase 1)	100 mg QD (Phase 1)	150 mg QD (Phase 1)	200 mg QD (Phase 1)	35 mg BID (Phase 1)	75 mg BID (Phase 1)	100 mg BID (Phase 1)
Number of subjects analysed	3	3	2	12	16	3	3	3	3	4
Units: ng/mL
geometric mean (geometric coefficient of variation)	50.80 ± 17	149.2 ± 71	99999 ± 99999	489.1 ± 45	595.5 ± 37	760.0 ± 58	1201 ± 19	202.2 ± 57	594.9 ± 27	507.2 ± 51

No statistical analyses for this end point

Secondary: Maximum Observed Plasma Concentration (Cmax) of PF-06463922 Following Multiple Oral Doses (Phase 1)

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End point title

Maximum Observed Plasma Concentration (Cmax) of PF-06463922 Following Multiple Oral Doses (Phase 1) ^[24]

End point description

Maximum Observed Plasma Concentration (Cmax) of PF-06463922 was observed directly from data. PK concentration analysis set for PF-06463922 included all subjects treated who had at least 1 concentration of PF-06463922. "99999" represents "not applicable" or "non evaluable" data.

End point type

Secondary

End point timeframe

Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24 hours post-dose on Cycle 1 Day 15 (24-hour samples not collected for BID groups).

Notes
[24] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: All other reporting arms are not applicable to this end point.

End point values	10 mg QD (Phase 1)	25 mg QD (Phase 1)	50 mg QD (Phase 1)	75 mg QD (Phase 1)	100 mg QD (Phase 1)	150 mg QD (Phase 1)	200 mg QD (Phase 1)	35 mg BID (Phase 1)	75 mg BID (Phase 1)	100 mg BID (Phase 1)
Number of subjects analysed	3	3	3	12	16	3	3	3	3	3
Units: ng/mL
geometric mean (geometric coefficient of variation)	67.29 ± 18	138.1 ± 35	359.7 ± 27	429.6 ± 48	550.2 ± 32	541.0 ± 42	99999 ± 99999	99999 ± 99999	550.0 ± 23	600.5 ± 27

No statistical analyses for this end point

Secondary: Time for Cmax (Tmax) of PF-06463922 Following Single Oral Doses (Phase 1)

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End point title

Time for Cmax (Tmax) of PF-06463922 Following Single Oral Doses (Phase 1) ^[25]

End point description

Tmax of PF-06463922 was observed directly from data as time of first occurrence. PK parameter analysis set for PF-06463922 included all enrolled subjects who received at least 1 dose of PF-06463922 and had sufficient information to estimate at least one of the PK parameters of interest for PF-06463922.

End point type

Secondary

End point timeframe

Notes
[25] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: All other reporting arms are not applicable to this end point.

End point values	10 mg QD (Phase 1)	25 mg QD (Phase 1)	50 mg QD (Phase 1)	75 mg QD (Phase 1)	100 mg QD (Phase 1)	150 mg QD (Phase 1)	200 mg QD (Phase 1)	35 mg BID (Phase 1)	75 mg BID (Phase 1)	100 mg BID (Phase 1)
Number of subjects analysed	3	3	2	12	16	3	3	3	3	4
Units: hours
median (full range (min-max))	1.98 (1.00 to 2.97)	2.00 (0.50 to 2.05)	1.25 (0.50 to 2.00)	1.09 (0.50 to 4.03)	1.96 (0.517 to 4.33)	1.05 (1.00 to 3.00)	2.00 (1.18 to 3.00)	1.20 (0.50 to 1.97)	1.23 (1.00 to 2.00)	2.00 (1.10 to 3.07)

No statistical analyses for this end point

Secondary: Time for Cmax (Tmax) of PF-06463922 Following Multiple Oral Doses (Phase 1)

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End point title

Time for Cmax (Tmax) of PF-06463922 Following Multiple Oral Doses (Phase 1) ^[26]

End point description

End point type

Secondary

End point timeframe

Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24 hours post-dose on Cycle 1 Day 15 (24-hour samples not collected for BID groups).

Notes
[26] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: All other reporting arms are not applicable to this end point.

End point values	10 mg QD (Phase 1)	25 mg QD (Phase 1)	50 mg QD (Phase 1)	75 mg QD (Phase 1)	100 mg QD (Phase 1)	150 mg QD (Phase 1)	200 mg QD (Phase 1)	35 mg BID (Phase 1)	75 mg BID (Phase 1)	100 mg BID (Phase 1)
Number of subjects analysed	3	3	3	12	16	3	3	3	3	3
Units: hours
median (full range (min-max))	1.00 (1.00 to 1.08)	1.00 (1.00 to 2.00)	2.00 (1.92 to 2.75)	1.03 (0.50 to 2.00)	1.13 (1.00 to 4.00)	1.30 (1.00 to 24.0)	1.61 (1.22 to 2.00)	0.50 (0.50 to 0.50)	0.55 (0.50 to 2.05)	2.00 (1.00 to 2.00)

No statistical analyses for this end point

Secondary: Area under the Plasma Concentration-Time profile from Time Zero to Time Tau (AUCtau) of PF-06463922 Following Single Oral Doses (Phase 1)

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End point title

Area under the Plasma Concentration-Time profile from Time Zero to Time Tau (AUCtau) of PF-06463922 Following Single Oral Doses (Phase 1) ^[27]

End point description

Tau refers to the dosing interval, and it equals to 12 or 24 hours for BID or QD dosing, respectively. AUCtau was determined using linear/log trapezoidal method. PK parameter analysis set for PF-06463922 included all enrolled subjects who received at least 1 dose of PF-06463922 and had sufficient information to estimate at least one of the PK parameters of interest for PF-06463922. "99999" represents "not applicable" or "non evaluable" data.

End point type

Secondary

End point timeframe

Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post-dose on Cylce 1 Day 1 for 25 mg QD and 150 mg QD groups; pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post-dose on Day -7 for all other groups.

Notes
[27] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: All other reporting arms are not applicable to this end point.

End point values	10 mg QD (Phase 1)	25 mg QD (Phase 1)	50 mg QD (Phase 1)	75 mg QD (Phase 1)	100 mg QD (Phase 1)	150 mg QD (Phase 1)	200 mg QD (Phase 1)	35 mg BID (Phase 1)	75 mg BID (Phase 1)	100 mg BID (Phase 1)
Number of subjects analysed	3	3	2	12	16	3	3	3	3	4
Units: nanogramhour/milliliter (nghr/mL)
geometric mean (geometric coefficient of variation)	488.2 ± 21	1387 ± 35	99999 ± 99999	3990 ± 55	5110 ± 28	7474 ± 73	11410 ± 43	982.4 ± 9	2996 ± 20	2925 ± 47

No statistical analyses for this end point

Secondary: Area under the Plasma Concentration-Time profile from Time Zero to Time Tau (AUCtau) of PF-06463922 Following Multiple Oral Doses (Phase 1)

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End point title

Area under the Plasma Concentration-Time profile from Time Zero to Time Tau (AUCtau) of PF-06463922 Following Multiple Oral Doses (Phase 1) ^[28]

End point description

End point type

Secondary

End point timeframe

Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24 hours post-dose on Cycle 1 Day 15 (24-hour samples not collected for BID groups)

Notes
[28] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: All other reporting arms are not applicable to this end point.

End point values	10 mg QD (Phase 1)	25 mg QD (Phase 1)	50 mg QD (Phase 1)	75 mg QD (Phase 1)	100 mg QD (Phase 1)	150 mg QD (Phase 1)	200 mg QD (Phase 1)	35 mg BID (Phase 1)	75 mg BID (Phase 1)	100 mg BID (Phase 1)
Number of subjects analysed	3	3	3	12	16	3	2	1	3	3
Units: ng*hr/mL
geometric mean (geometric coefficient of variation)	752.1 ± 26	1701 ± 29	3367 ± 39	4107 ± 53	5121 ± 30	6157 ± 9	99999 ± 99999	99999 ± 99999	3574 ± 35	4058 ± 33

No statistical analyses for this end point

Secondary: Area under the Plasma Concentration-Time Profile from Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06463922 Following Single Oral Doses (Phase 1)

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End point title

Area under the Plasma Concentration-Time Profile from Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06463922 Following Single Oral Doses (Phase 1) ^[29]

End point description

AUCinf was calculated as AUClast + (Clast*/kel), where AUClast was the area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration, Clast* was the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis, and kel was the rate constant for terminal phase. PK parameter analysis set for PF-06463922 included all enrolled subjects who received at least 1 dose of PF-06463922 and had sufficient information to estimate at least one of the PK parameters of interest for PF-06463922. "99999" represents "not applicable" or "non evaluable" data.

End point type

Secondary

End point timeframe

Notes
[29] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: All other reporting arms are not applicable to this end point.

End point values	10 mg QD (Phase 1)	50 mg QD (Phase 1)	75 mg QD (Phase 1)	100 mg QD (Phase 1)	200 mg QD (Phase 1)	35 mg BID (Phase 1)	75 mg BID (Phase 1)	100 mg BID (Phase 1)
Number of subjects analysed	1	2	11	15	3	2	1	4
Units: ng*hr/mL
geometric mean (geometric coefficient of variation)	99999 ± 99999	99999 ± 99999	7663 ± 79	8236 ± 25	18340 ± 61	99999 ± 99999	99999 ± 99999	6318 ± 56

No statistical analyses for this end point

Secondary: Apparent Oral Clearance (CL/F) of PF-06463922 Following Single Oral Doses (Phase 1)

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End point title

Apparent Oral Clearance (CL/F) of PF-06463922 Following Single Oral Doses (Phase 1) ^[30]

End point description

Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. CL/F was calculated as dose/AUCinf, where AUCinf was the area under the plasma concentration-time profile from time 0 extrapolated to infinite time. PK parameter analysis set for PF-06463922 included all enrolled subjects who received at least 1 dose of PF-06463922 and had sufficient information to estimate at least one of the PK parameters of interest for PF-06463922. "99999" represents "not applicable" or "non evaluable" data.

End point type

Secondary

End point timeframe

Notes
[30] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: All other reporting arms are not applicable to this end point.

End point values	10 mg QD (Phase 1)	50 mg QD (Phase 1)	75 mg QD (Phase 1)	100 mg QD (Phase 1)	200 mg QD (Phase 1)	35 mg BID (Phase 1)	75 mg BID (Phase 1)	100 mg BID (Phase 1)
Number of subjects analysed	1	2	11	15	3	2	1	4
Units: liter/hour (L/hr)
geometric mean (geometric coefficient of variation)	99999 ± 99999	99999 ± 99999	9.788 ± 79	12.14 ± 25	10.90 ± 61	99999 ± 99999	99999 ± 99999	15.83 ± 56

No statistical analyses for this end point

Secondary: Apparent Oral Clearance (CL/F) of PF-06463922 Following Multiple Oral Doses (Phase 1)

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End point title

Apparent Oral Clearance (CL/F) of PF-06463922 Following Multiple Oral Doses (Phase 1) ^[31]

End point description

End point type

Secondary

End point timeframe

Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24 hours post-dose on Cycle 1 Day 15 (24-hour samples not collected for BID groups)

Notes
[31] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: All other reporting arms are not applicable to this end point.

End point values	10 mg QD (Phase 1)	25 mg QD (Phase 1)	50 mg QD (Phase 1)	75 mg QD (Phase 1)	100 mg QD (Phase 1)	150 mg QD (Phase 1)	200 mg QD (Phase 1)	35 mg BID (Phase 1)	75 mg BID (Phase 1)	100 mg BID (Phase 1)
Number of subjects analysed	3	3	3	12	16	3	2	1	3	3
Units: L/hr
geometric mean (geometric coefficient of variation)	13.27 ± 26	14.72 ± 29	14.84 ± 39	17.66 ± 48	19.52 ± 30	24.37 ± 9	99999 ± 99999	99999 ± 99999	20.99 ± 35	22.37 ± 47

No statistical analyses for this end point

Secondary: Apparent Volume of Distribution (Vz/F) of PF-06463922 Following Single Oral Doses (Phase 1)

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End point title

Apparent Volume of Distribution (Vz/F) of PF-06463922 Following Single Oral Doses (Phase 1) ^[32]

End point description

Vz/F was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug, and calculated as dose/(AUCinf*kel), where AUCinf was the area under the plasma concentration-time profile from time 0 extrapolated to infinite time, kel was the rate constant for terminal phase. PK parameter analysis set for PF-06463922 included all enrolled subjects who received at least 1 dose of PF-06463922 and had sufficient information to estimate at least one of the PK parameters of interest for PF-06463922. "99999" represents "not applicable" or "non evaluable" data.

End point type

Secondary

End point timeframe

Notes
[32] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: All other reporting arms are not applicable to this end point.

End point values	10 mg QD (Phase 1)	50 mg QD (Phase 1)	75 mg QD (Phase 1)	100 mg QD (Phase 1)	200 mg QD (Phase 1)	35 mg BID (Phase 1)	75 mg BID (Phase 1)	100 mg BID (Phase 1)
Number of subjects analysed	1	2	11	15	3	2	1	4
Units: liters (L)
geometric mean (geometric coefficient of variation)	99999 ± 99999	99999 ± 99999	367.9 ± 54	356.3 ± 39	307.8 ± 41	99999 ± 99999	99999 ± 99999	378.3 ± 54

No statistical analyses for this end point

Secondary: Observed Accumulation Ratio (Rac) of PF-06463922 Following Multiple Oral Doses (Phase 1)

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End point title

Observed Accumulation Ratio (Rac) of PF-06463922 Following Multiple Oral Doses (Phase 1) ^[33]

End point description

Rac was calculated as Day 15 AUCtau/Day -7 AUCtau or Day 1 AUCtau, where AUCtau was the area under the plasma concentration-time profile from time 0 to time tau (12 and 24 hours for BID and QD dosing regimen, respectively). PK parameter analysis set for PF-06463922 included all enrolled subjects who received at least 1 dose of PF-06463922 and had sufficient information to estimate at least one of the PK parameters of interest for PF-06463922. "99999" represents "not applicable" or "non evaluable" data.

End point type

Secondary

End point timeframe

Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24 hours post-dose on Cycle 1 Day 15 (24-hour samples not collected for BID groups)

Notes
[33] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: All other reporting arms are not applicable to this end point.

End point values	10 mg QD (Phase 1)	25 mg QD (Phase 1)	50 mg QD (Phase 1)	75 mg QD (Phase 1)	100 mg QD (Phase 1)	150 mg QD (Phase 1)	200 mg QD (Phase 1)	35 mg BID (Phase 1)	75 mg BID (Phase 1)	100 mg BID (Phase 1)
Number of subjects analysed	3	3	2	12	15	3	2	1	3	3
Units: ratio
arithmetic mean (standard deviation)	1.543 ± 0.075056	1.237 ± 0.20817	1.105 ± 99999	1.121 ± 0.44575	1.071 ± 0.31138	1.000 ± 0.79137	0.6500 ± 99999	99999 ± 99999	1.231 ± 0.35228	1.523 ± 0.29569

No statistical analyses for this end point

Secondary: Terminal Half-Life of PF-06463922 Following Single Oral Doses (Phase 1)

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End point title

Terminal Half-Life of PF-06463922 Following Single Oral Doses (Phase 1) ^[34]

End point description

Terminal plasma half-life was defined as the time measured for the plasma concentration to decrease by one half, and calculated as loge(2)/kel, where kel was the rate constant for terminal phase. PK parameter analysis set for PF-06463922 included all enrolled subjects who received at least 1 dose of PF-06463922 and had sufficient information to estimate at least one of the PK parameters of interest for PF-06463922. "99999" represents "not applicable" or "non evaluable" data.

End point type

Secondary

End point timeframe

Notes
[34] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: All other reporting arms are not applicable to this end point.

End point values	10 mg QD (Phase 1)	50 mg QD (Phase 1)	75 mg QD (Phase 1)	100 mg QD (Phase 1)	200 mg QD (Phase 1)	35 mg BID (Phase 1)	75 mg BID (Phase 1)	100 mg BID (Phase 1)
Number of subjects analysed	1	2	11	15	3	2	1	4
Units: hours (hr)
arithmetic mean (standard deviation)	99999 ± 99999	23.70 ± 99999	27.22 ± 8.2961	20.89 ± 5.0308	19.80 ± 3.3045	25.55 ± 99999	99999 ± 99999	17.18 ± 5.1874

No statistical analyses for this end point

Secondary: Steady State Accumulation Ratio (Rss) of PF-06463922 Following Multiple Oral Doses (Phase 1)

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End point title

Steady State Accumulation Ratio (Rss) of PF-06463922 Following Multiple Oral Doses (Phase 1) ^[35]

End point description

Rss was calculated as Day 15 AUCtau/Day -7 AUCinf, where AUCtau was the area under the plasma concentration-time profile from time 0 to time tau (12 and 24 hours for BID and QD dosing regimen, respectively), and AUCinf was the area under the plasma concentration-time profile from time 0 extrapolated to infinite time. PK parameter analysis set for PF-06463922 included all enrolled subjects who received at least 1 dose of PF-06463922 and had sufficient information to estimate at least one of the PK parameters of interest for PF-06463922. "99999" represents "not applicable" or "non evaluable" data.

End point type

Secondary

End point timeframe

Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24 hours post-dose on Cycle 1 Day 15 (24-hour samples not collected for BID groups)

Notes
[35] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: All other reporting arms are not applicable to this end point.

End point values	10 mg QD (Phase 1)	50 mg QD (Phase 1)	75 mg QD (Phase 1)	100 mg QD (Phase 1)	200 mg QD (Phase 1)	35 mg BID (Phase 1)	75 mg BID (Phase 1)	100 mg BID (Phase 1)
Number of subjects analysed	1	2	11	14	2	1	1	3
Units: ratio
arithmetic mean (standard deviation)	99999 ± 99999	0.5600 ± 99999	0.6131 ± 0.29021	0.6603 ± 0.18604	0.3935 ± 99999	99999 ± 99999	99999 ± 99999	0.7687 ± 0.13552

No statistical analyses for this end point

Secondary: Renal Clearance (CLr) of PF-06463922 (Phase 1)

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End point title

Renal Clearance (CLr) of PF-06463922 (Phase 1) ^[36]

End point description

Renal clearance was calculated as Aetau/AUCtau, where Aetau was the cumulative amount of drug recovered unchanged in urine up to dosing interval tau (24 hours for QD dosing regimen), and AUCtau was the area under the plasma concentration-time profile from time 0 to time tau (24 hours for QD dosing regimen). PK parameter analysis set for PF-06463922 included all enrolled subjects who received at least 1 dose of PF-06463922 and had sufficient information to estimate at least one of the PK parameters of interest for PF-06463922. This end point is only applicable to 100 mg QD group.

End point type

Secondary

End point timeframe

0-4 hours, 4-12 hours and 12-24 hours post-dose on Cycle 1 Day 15

Notes
[36] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: All other reporting arms are not applicable to this end point.

End point values	100 mg QD (Phase 1)
Number of subjects analysed	3
Units: ml/hour
geometric mean (geometric coefficient of variation)	61.31 ± 58

No statistical analyses for this end point

Secondary: Percent of PF-06463922 Recovered Unchanged in Urine up to Dosing Interval (AEtau%) (Phase 1)

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End point title

Percent of PF-06463922 Recovered Unchanged in Urine up to Dosing Interval (AEtau%) (Phase 1) ^[37]

End point description

Dosing interval was 24 hours for QD dosing regimen. Aetau% was calculated as 100*Ae24/dose, where Ae24 was the cumulative amount of drug recovered unchanged in urine up to 24 hours post-dose. PK parameter analysis set for PF-06463922 included all enrolled subjects who received at least 1 dose of PF-06463922 and had sufficient information to estimate at least one of the PK parameters of interest for PF-06463922. This end point is only applicable to 100 mg QD group.

End point type

Secondary

End point timeframe

0-4 hours, 4-12 hours and 12-24 hours post-dose on Cycle 1 Day 15

Notes
[37] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: All other reporting arms are not applicable to this end point.

End point values	100 mg QD (Phase 1)
Number of subjects analysed	3
Units: percentage
arithmetic mean (standard deviation)	0.4017 ± 0.11074

No statistical analyses for this end point

Secondary: Maximum Observed Plasma Concentration (Cmax) of Midazolam (Phase 1)

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End point title

Maximum Observed Plasma Concentration (Cmax) of Midazolam (Phase 1) ^[38]

End point description

Cmax of midazolam was observed directly from data. Only subjects in 25 mg and 150 mg QD groups were given midazolam. Day -7 data reflect the PK assessment before administration of PF-06463922, and Cycle 1 Day 15 data reflect the PK assessment after multiple doses of PF-06463922 were administered. PK concentration analysis set for midazolam included all subjects treated with midazolam who had at least 1 concentration of midazolam.

End point type

Secondary

End point timeframe

Pre-dose, 0.5, 1, 2, 4, 6, 8, 9 and 24 hours post-dose on Day -7 and pre-dose, 0.5, 1, 2, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 15

Notes
[38] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: All other reporting arms are not applicable to this end point.

End point values	25 mg QD (Phase 1)	150 mg QD (Phase 1)
Number of subjects analysed	3	3
Units: ng/mL
geometric mean (geometric coefficient of variation)
Day -7\|	16.06 ± 42	11.56 ± 48
Cycle 1 Day 15\|	9.697 ± 40	5.734 ± 43

No statistical analyses for this end point

Secondary: Time for Cmax (Tmax) of Midazolam (Phase 1)

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End point title

Time for Cmax (Tmax) of Midazolam (Phase 1) ^[39]

End point description

Tmax of midazolam was observed directly from data as time of first occurrence. Only subjects in 25 mg and 150 mg QD groups were given midazolam. Day -7 data reflect the PK assessment before administration of PF-06463922, and Cycle 1 Day 15 data reflect the PK assessment after multiple doses of PF-06463922 were administered. PK parameter analysis set for midazolam included all subjects who received at least 1 dose of midazolam and for which at least 1 midazolam PK parameter of interest was available.

End point type

Secondary

End point timeframe

Pre-dose, 0.5, 1, 2, 4, 6, 8, 9 and 24 hours post-dose on Day -7 and pre-dose, 0.5, 1, 2, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 15

Notes
[39] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: All other reporting arms are not applicable to this end point.

End point values	25 mg QD (Phase 1)	150 mg QD (Phase 1)
Number of subjects analysed	3	3
Units: hours
median (full range (min-max))
Day -7\|	0.50 (0.50 to 1.00)	0.50 (0.50 to 0.50)
Cycle 1 Day 15\|	0.50 (0.50 to 1.00)	0.50 (0.50 to 0.533)

No statistical analyses for this end point

Secondary: Area under the Plasma Concentration-Time profile from Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Midazolam (Phase 1)

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End point title

Area under the Plasma Concentration-Time profile from Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Midazolam (Phase 1) ^[40]

End point description

Area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration (AUClast) of midazolam was determined using linear/log trapezoidal method. Only subjects in 25 mg and 150 mg QD groups were given midazolam. Day -7 data reflect the PK assessment before administration of PF-06463922, and Cycle 1 Day 15 data reflect the PK assessment after multiple doses of PF-06463922 were administered. PK parameter analysis set for midazolam included all subjects who received at least 1 dose of midazolam and for which at least 1 midazolam PK parameter of interest was available.

End point type

Secondary

End point timeframe

Pre-dose, 0.5, 1, 2, 4, 6, 8, 9 and 24 hours post-dose on Day -7 and pre-dose, 0.5, 1, 2, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 15

Notes
[40] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: All other reporting arms are not applicable to this end point.

End point values	25 mg QD (Phase 1)	150 mg QD (Phase 1)
Number of subjects analysed	3	3
Units: ng*hr/mL
geometric mean (geometric coefficient of variation)
Day -7\|	51.30 ± 47	36.49 ± 20
Cycle 1 Day 15\|	20.43 ± 18	14.44 ± 25

No statistical analyses for this end point

Secondary: Area under the Plasma Concentration-Time Profile from Time Zero Extrapolated to Infinite Time (AUCinf) of Midazolam (Phase 1)

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End point title

Area under the Plasma Concentration-Time Profile from Time Zero Extrapolated to Infinite Time (AUCinf) of Midazolam (Phase 1) ^[41]

End point description

AUCinf was calculated as AUClast + (Clast*/kel), where AUClast was the area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration, Clast* was the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis, and kel was the rate constant for terminal phase. Only subjects in 25 mg and 150 mg QD groups were given midazolam. Day -7 data reflect the PK assessment before administration of PF-06463922, and Cycle 1 Day 15 data reflect the PK assessment after multiple doses of PF-06463922 were administered. PK parameter analysis set for midazolam included all subjects who received at least 1 dose of midazolam and for which at least 1 midazolam PK parameter of interest was available. "99999" represents "not applicable" or "non evaluable" data.

End point type

Secondary

End point timeframe

Pre-dose, 0.5, 1, 2, 4, 6, 8, 9 and 24 hours post-dose on Day -7 and pre-dose, 0.5, 1, 2, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 15

Notes
[41] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: All other reporting arms are not applicable to this end point.

End point values	25 mg QD (Phase 1)	150 mg QD (Phase 1)
Number of subjects analysed	3	3 ^[42]
Units: ng*hr/mL
geometric mean (geometric coefficient of variation)
Day -7\|	54.53 ± 43	99999 ± 99999
Cycle 1 Day 15\|	21.32 ± 18	16.09 ± 29

Notes
[42] - Number of subjects contributing to Day -7 data is 2.

No statistical analyses for this end point

Secondary: Apparent Oral Clearance (CL/F) of Midazolam (Phase 1)

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End point title

Apparent Oral Clearance (CL/F) of Midazolam (Phase 1) ^[43]

End point description

Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. CL/F was calculated as dose/AUCinf, where AUCinf was the area under the plasma concentration-time profile from time 0 extrapolated to infinite time. Only subjects in 25 mg and 150 mg QD groups were given midazolam. Day -7 data reflect the PK assessment before administration of PF-06463922, and Cycle 1 Day 15 data reflect the PK assessment after multiple doses of PF-06463922 were administered. PK parameter analysis set for midazolam included all subjects who received at least 1 dose of midazolam and for which at least 1 midazolam PK parameter of interest was available. "99999" represents "not applicable" or "non evaluable" data.

End point type

Secondary

End point timeframe

Pre-dose, 0.5, 1, 2, 4, 6, 8, 9 and 24 hours post-dose on Day -7 and pre-dose, 0.5, 1, 2, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 15

Notes
[43] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: All other reporting arms are not applicable to this end point.

End point values	25 mg QD (Phase 1)	150 mg QD (Phase 1)
Number of subjects analysed	3	3 ^[44]
Units: L/hr
geometric mean (geometric coefficient of variation)
Day -7\|	36.68 ± 43	99999 ± 99999
Cycle 1 Day 15\|	93.86 ± 18	124.2 ± 29

Notes
[44] - Number of subjects contributing to Day -7 data is 2.

No statistical analyses for this end point

Secondary: Apparent Volume of Distribution (Vz/F) of Midazolam (Phase 1)

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End point title

Apparent Volume of Distribution (Vz/F) of Midazolam (Phase 1) ^[45]

End point description

Vz/F was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug, and calculated as dose/(AUCinf*kel), where AUCinf was the area under the plasma concentration-time profile from time 0 extrapolated to infinite time, kel was the rate constant for terminal phase. Only subjects in 25 mg and 150 mg QD groups were given midazolam. Day -7 data reflect the PK assessment before administration of PF-06463922, and Cycle 1 Day 15 data reflect the PK assessment after multiple doses of PF-06463922 were administered. PK parameter analysis set for midazolam included all subjects who received at least 1 dose of midazolam and for which at least 1 midazolam PK parameter of interest was available. "99999" represents "not applicable" or "non evaluable" data.

End point type

Secondary

End point timeframe

Pre-dose, 0.5, 1, 2, 4, 6, 8, 9 and 24 hours post-dose on Day -7 and pre-dose, 0.5, 1, 2, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 15

Notes
[45] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: All other reporting arms are not applicable to this end point.

End point values	25 mg QD (Phase 1)	150 mg QD (Phase 1)
Number of subjects analysed	3	3 ^[46]
Units: liter
geometric mean (geometric coefficient of variation)
Day -7\|	229.0 ± 7	99999 ± 99999
Cycle 1 Day 15\|	404.4 ± 51	702.2 ± 100

Notes
[46] - Number of subjects contributing to Day -7 data is 2.

No statistical analyses for this end point

Secondary: Terminal Half-Life of Midazolam (Phase 1)

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End point title

Terminal Half-Life of Midazolam (Phase 1) ^[47]

End point description

Terminal plasma half-life was defined as the time measured for the plasma concentration to decrease by one half, and calculated as loge(2)/kel, where kel was the rate constant for terminal phase. Only subjects in 25 mg and 150 mg QD groups were given midazolam. Day -7 data reflect the PK assessment before administration of PF-06463922, and Cycle 1 Day 15 data reflect the PK assessment after multiple doses of PF-06463922 were administered. PK parameter analysis set for midazolam included all subjects who received at least 1 dose of midazolam and for which at least 1 midazolam PK parameter of interest was available. "99999" represents "not applicable" or "non evaluable" data.

End point type

Secondary

End point timeframe

Pre-dose, 0.5, 1, 2, 4, 6, 8, 9 and 24 hours post-dose on Day -7 and pre-dose, 0.5, 1, 2, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 15

Notes
[47] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: All other reporting arms are not applicable to this end point.

End point values	25 mg QD (Phase 1)	150 mg QD (Phase 1)
Number of subjects analysed	3	3 ^[48]
Units: hr
arithmetic mean (standard deviation)
Day -7\|	4.620 ± 1.9328	5.120 ± 99999
Cycle 1 Day 15\|	3.343 ± 2.0358	5.257 ± 5.0639

Notes
[48] - Number of subjects contributing to Day -7 data is 2.

No statistical analyses for this end point

Secondary: Number of Subjects with ALK Mutation Based on Plasma CNA Analysis (Phase 1)

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End point title

Number of Subjects with ALK Mutation Based on Plasma CNA Analysis (Phase 1)

End point description

Plasma circulating nucleic acid (CNA) samples were analyzed for ALK kinase domain mutations by digital polymerase chain reaction (PCR) BEAMing technology. Number of subjects with one or more ALK mutations is presented. CNA peripheral blood analysis set included all subjects of the ITT analysis set who had at least 1 molecular biomarker assayed.

End point type

Secondary

End point timeframe

Screening

End point values	ALK Positive Population (Phase 1)
Number of subjects analysed	39
Units: subjects	14

No statistical analyses for this end point

Secondary: Number of Subjects with ALK Mutation Based on Tumor Tissue Analysis (Phase 1)

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End point title

Number of Subjects with ALK Mutation Based on Tumor Tissue Analysis (Phase 1)

End point description

Tumor tissues from archived tissue specimens and/or a de novo biopsy were analyzed for ALK kinase domain mutations. Number of subjects with one or more ALK mutations is presented. Tumor Tissue analysis set included all subjects of the ITT analysis set who had at least 1 molecular tumor biomarker assayed from either the screening archival or screening de novo tumor biopsy sample (or both).

End point type

Secondary

End point timeframe

Screening

End point values	ALK Positive Population (Phase 1)
Number of subjects analysed	30
Units: subjects	7

No statistical analyses for this end point

Secondary: Number of Subjects Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 1)

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End point title

Number of Subjects Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 1)

End point description

European Organisation for Research and Treatment of Cancer Core Quality of Life Questionaires (EORTC QLQ)-C30 (v3.0) consists of 30 questions for 5 functional domains (physical, role, emotional, cognitive, social), global quality of life (QoL), disease/treatment related symptoms (fatigue, nausea/vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea), and the perceived financial impact of disease. Each scale was transformed to a range of 0 to 100 using EORTC algorithm. For global QoL and functional scales, higher score means better performance, improvement was an increase of at least 10 points, worsening was a decrease of at least 10 points. For symptom scales, higher score means worse symptoms, improvement was a decrease of at least 10 points, worsening was an increase of at least 10 points. Patient reported outcome (PRO) set included all subjects who received at least 1 dose of PF-06463922, completed a baseline and at least 1 post-baseline assessment.

End point type

Secondary

End point timeframe

3 years

End point values	Phase 1 PRO Evaluable Population
Number of subjects analysed	43
Units: subjects
Improved in global QoL\|	20
Stable in global QoL\|	13
Worsened in global QoL\|	10
Improved in physical functioning\|	6
Stable in physical functioning\|	30
Worsened in physical functioning\|	7
Improved in role functioning\|	15
Stable in role functioning\|	16
Worsened in role functioning\|	12
Improved in emotional functioning\|	15
Stable in emotional functioning\|	20
Worsened in emotional functioning\|	8
Improved in cognitive functioning\|	8
Stable in cognitive functioning\|	21
Worsened in cognitive functioning\|	14
Improved in social functioning\|	13
Stable in social functioning\|	18
Worsened in social functioning\|	12
Improved in fatigue\|	18
Stable in fatigue\|	19
Worsened in fatigue\|	6
Improved in nausea and vomiting\|	10
Stable in nausea and vomiting\|	32
worsened in nausea and vomiting\|	1
Improved in pain\|	18
Stable in pain\|	15
Worsened in pain\|	10
Improved in dyspnea\|	13
Stable in dyspnea\|	19
Worsened in dyspnea\|	11
Improved in insomnia\|	19
Stable in insomnia\|	17
Worsened in insomnia\|	7
Improved in appetite loss\|	14
Stable in appetite loss\|	27
Worsened in appetite loss\|	2
Improved in constipation\|	11
Stable in constipation\|	27
Worsened in constipation\|	5
Improved in diarrhea\|	9
Stable in diarrhea\|	29
Worsened in diarrhea\|	5
Improved in financial difficulties\|	7
Stable in financial difficulties\|	21
Worsened in financial difficulties\|	15

No statistical analyses for this end point

Secondary: Number of Subjects Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 1)

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End point title

Number of Subjects Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 1)

End point description

EORTC QLQ-LC13 is the lung cancer module of EORTC QLQ-C30 and includes questions specific to the disease associated symptoms (dyspnea, cough, hemoptysis, and site specific pain), treatment-related symptoms (sore mouth, dysphagia, neuropathy and alopecia), and analgesic use of lung cancer patients. The scale was transformed to a range of 0 to 100 using standard EORTC algorithm. Higher score indicates worse symptoms, and improvement was defined as a decrease of at least 10 points, worsening was defined as an increase of at least 10 points. All scales which had not improved nor worsened were considered stable. Patient reported outcome (PRO) set included all subjects who received at least 1 dose of PF-06463922, completed a baseline and at least 1 post-baseline assessment.

End point type

Secondary

End point timeframe

3 years

End point values	Phase 1 PRO Evaluable Population
Number of subjects analysed	43 ^[49]
Units: subjects
Improved in dyspnea\|	10
Stable in dyspnea\|	22
Worsened in dyspnea\|	11
Improved in coughing\|	23
Stable in coughing\|	12
Worsened in coughing\|	8
Improved in hemoptysis\|	1
Stable in hemoptysis\|	42
Worsened in hemoptysis\|	0
Improved in sore mouth\|	0
Stable in sore mouth\|	40
Worsened in sore mouth\|	3
Improved in dysphagia\|	4
Stable in dysphagia\|	37
Worsened in dysphagia\|	2
Improved in peripheral neuropathy\|	6
Stable in peripheral neuropathy\|	19
Worsened in peripheral neuropathy\|	18
Improved in alopecia\|	3
Stable in alopecia\|	30
Worsened in alopecia\|	9
Improved in chest pain\|	16
Stable in chest pain\|	22
Worsened in chest pain\|	5
Improved in arm or shoulder pain\|	10
Stable in arm or shoulder pain\|	28
Worsened in arm or shoulder pain\|	5
Improved in pain in other parts\|	19
Stable in pain in other parts\|	14
Worsened in pain in other parts\|	10

Notes
[49] - Number of subjects analyzed for alopecia is 42.

No statistical analyses for this end point

Secondary: Change from Baseline in Mini Mental State Examination (MMSE) Score (Phase 1)

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End point title

Change from Baseline in Mini Mental State Examination (MMSE) Score (Phase 1) ^[50]

End point description

In Phase 1, the MMSE was collected to assess mental status. The MMSE is a 30 item questionnaire that tests 5 areas of cognitive function: orientation, registration, attention and calculation, recall and language. The maximum score is 30. A score of 23 or lower is indicative of cognitive impairment. The MMSE was removed under Amendment 6 of the study protocol, and not required for Phase 2, as the tool was not considered meaningful for assessment of cognitive function. MMSE assessment evaluable analysis set included all subjects who received at least 1 dose of PF-06463922 and completed a baseline and at least 1 post-baseline assessment. "99999" represents "not applicable" or "non evaluable data".

End point type

Secondary

End point timeframe

3 years

Notes
[50] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: All other reporting arms are not applicable to this end point.

End point values	10 mg QD (Phase 1)	25 mg QD (Phase 1)	50 mg QD (Phase 1)	75 mg QD (Phase 1)	100 mg QD (Phase 1)	150 mg QD (Phase 1)	200 mg QD (Phase 1)	35 mg BID (Phase 1)	75 mg BID (Phase 1)	100 mg BID (Phase 1)
Number of subjects analysed	2 ^[51]	3 ^[52]	3 ^[53]	9 ^[54]	16 ^[55]	3 ^[56]	2 ^[57]	2 ^[58]	3 ^[59]	4 ^[60]
Units: units on a score
arithmetic mean (standard deviation)
Cycle 1 Day 1\|	1.0 ± 1.41	99999 ± 99999	-0.5 ± 0.71	-0.9 ± 2.27	0.8 ± 1.39	99999 ± 99999	99999 ± 99999	99999 ± 99999	0.0 ± 99999	0.0 ± 99999
Cycle 2 Day 1\|	2.0 ± 99999	-0.3 ± 0.58	2.0 ± 99999	0.3 ± 1.41	0.0 ± 1.79	4.7 ± 8.08	4.0 ± 4.24	0.0 ± 0.00	0.0 ± 0.00	-0.3 ± 1.15
Cycle 3 Day 1\|	2.0 ± 0.00	0.3 ± 0.58	-0.5 ± 0.71	-0.6 ± 1.85	0.2 ± 1.52	5.0 ± 8.49	3.0 ± 2.83	99999 ± 99999	0.0 ± 99999	-1.0 ± 1.00
Cycle 4 Day 1\|	5.0 ± 99999	0.5 ± 0.71	1.5 ± 2.12	-1.1 ± 1.81	0.0 ± 1.47	2.0 ± 6.24	-0.5 ± 3.54	99999 ± 99999	0.0 ± 99999	-0.7 ± 1.15
Cycle 5 Day 1\|	0.5 ± 3.54	0.5 ± 0.71	1.5 ± 2.12	0.3 ± 1.25	-0.2 ± 1.72	4.7 ± 8.14	0.5 ± 6.36	99999 ± 99999	0.0 ± 99999	-0.5 ± 0.71
Cycle 6 Day 1\|	2.5 ± 2.12	0.5 ± 0.71	1.0 ± 1.41	-0.4 ± 2.70	0.3 ± 0.90	4.3 ± 5.86	2.0 ± 4.24	99999 ± 99999	0.0 ± 99999	-1.3 ± 2.31
Cycle 7 Day 1\|	2.0 ± 99999	0.5 ± 0.71	1.5 ± 2.12	-0.1 ± 1.21	0.4 ± 0.90	4.7 ± 8.33	3.0 ± 4.24	99999 ± 99999	0.0 ± 99999	-0.7 ± 1.15
Cycle 8 Day 1\|	-4.0 ± 99999	0.5 ± 0.71	1.5 ± 2.12	-0.1 ± 2.34	0.2 ± 1.34	3.0 ± 7.81	4.0 ± 4.24	99999 ± 99999	0.0 ± 99999	0.0 ± 0.00
Cycle 9 Day 1\|	99999 ± 99999	0.0 ± 0.00	0.0 ± 99999	-1.0 ± 2.31	0.3 ± 2.10	6.0 ± 8.49	6.0 ± 99999	99999 ± 99999	99999 ± 99999	-0.3 ± 0.58
Cycle 10 Day 1\|	-5.0 ± 99999	0.5 ± 0.71	0.0 ± 99999	0.0 ± 0.00	-0.1 ± 0.88	6.5 ± 9.19	6.0 ± 99999	99999 ± 99999	0.0 ± 99999	-1.7 ± 1.53
Cycle 11 Day 1\|	99999 ± 99999	-0.5 ± 0.71	0.0 ± 99999	0.3 ± 1.70	-0.2 ± 1.53	7.0 ± 8.49	3.5 ± 3.54	99999 ± 99999	0.0 ± 99999	0.0 ± 0.00
Cycle 12 Day 1\|	99999 ± 99999	0.5 ± 0.71	99999 ± 99999	-0.6 ± 2.19	-0.2 ± 2.33	6.5 ± 9.19	3.5 ± 3.54	99999 ± 99999	0.0 ± 99999	-0.7 ± 0.58
Cycle 13 Day 1\|	99999 ± 99999	0.5 ± 0.71	99999 ± 99999	0.8 ± 1.79	0.5 ± 2.22	5.5 ± 7.78	3.0 ± 4.24	99999 ± 99999	0.0 ± 99999	-0.5 ± 0.71
Cycle 14 Day 1\|	99999 ± 99999	0.5 ± 0.71	99999 ± 99999	-0.3 ± 3.20	0.3 ± 0.79	6.0 ± 8.49	2.5 ± 3.54	99999 ± 99999	0.0 ± 99999	0.0 ± 0.00
Cycle 15 Day 1\|	99999 ± 99999	0.5 ± 0.71	99999 ± 99999	-1.7 ± 5.43	0.1 ± 1.36	99999 ± 99999	4.0 ± 4.24	99999 ± 99999	0.0 ± 99999	-0.3 ± 0.58
Cycle 16 Day 1\|	99999 ± 99999	0.0 ± 1.41	99999 ± 99999	-0.2 ± 2.49	-0.2 ± 1.99	1.0 ± 99999	1.5 ± 6.36	99999 ± 99999	0.0 ± 99999	0.0 ± 0.00
Cycle 17 Day 1\|	99999 ± 99999	-2.0 ± 2.83	99999 ± 99999	0.6 ± 1.95	0.1 ± 1.17	-3.0 ± 99999	4.0 ± 4.24	99999 ± 99999	0.0 ± 99999	-1.3 ± 1.53
Cycle 18 Day 1\|	99999 ± 99999	-0.5 ± 0.71	99999 ± 99999	0.8 ± 1.79	0.0 ± 1.73	-2.0 ± 99999	3.0 ± 4.24	99999 ± 99999	99999 ± 99999	0.0 ± 0.00
Cycle 19 Day 1\|	99999 ± 99999	-0.5 ± 0.71	99999 ± 99999	0.8 ± 1.79	-0.6 ± 2.65	0.0 ± 99999	3.5 ± 4.95	99999 ± 99999	0.0 ± 99999	-0.5 ± 0.71
Cycle 20 Day 1\|	99999 ± 99999	0.0 ± 0.00	99999 ± 99999	0.0 ± 1.41	0.7 ± 2.12	0.0 ± 99999	3.5 ± 3.54	99999 ± 99999	0.0 ± 99999	-0.5 ± 0.71
Cycle 21 Day 1\|	99999 ± 99999	-0.5 ± 0.71	99999 ± 99999	0.0 ± 1.41	0.1 ± 2.09	99999 ± 99999	4.0 ± 4.24	99999 ± 99999	0.0 ± 99999	-0.5 ± 0.71
Cycle 22 Day 1\|	99999 ± 99999	0.0 ± 0.00	99999 ± 99999	0.4 ± 1.52	0.1 ± 1.45	0.0 ± 99999	3.5 ± 3.54	99999 ± 99999	-1.0 ± 99999	-0.3 ± 0.58
Cycle 23 Day 1\|	99999 ± 99999	0.5 ± 0.71	99999 ± 99999	0.0 ± 1.41	0.1 ± 1.81	-1.0 ± 99999	1.5 ± 3.54	99999 ± 99999	0.0 ± 99999	-2.3 ± 4.04
Cycle 24 Day 1\|	99999 ± 99999	0.5 ± 0.71	99999 ± 99999	-0.4 ± 0.89	0.6 ± 0.74	1.0 ± 99999	1.5 ± 4.95	99999 ± 99999	0.0 ± 99999	0.0 ± 0.00
Cycle 25 Day 1\|	99999 ± 99999	0.0 ± 0.00	99999 ± 99999	0.8 ± 1.79	-0.9 ± 2.27	-2.0 ± 99999	2.5 ± 4.95	99999 ± 99999	0.0 ± 99999	0.0 ± 0.00
Cycle 26 Day 1\|	99999 ± 99999	0.5 ± 0.71	99999 ± 99999	0.8 ± 1.79	-0.4 ± 2.77	-1.0 ± 99999	2.0 ± 4.24	99999 ± 99999	0.0 ± 99999	-0.3 ± 0.58
Cycle 27 Day 1\|	99999 ± 99999	0.5 ± 0.71	99999 ± 99999	0.8 ± 1.79	-0.1 ± 2.67	-1.0 ± 99999	3.5 ± 3.54	99999 ± 99999	0.0 ± 99999	-1.0 ± 1.41
Cycle 28 Day 1\|	99999 ± 99999	0.5 ± 0.71	99999 ± 99999	1.0 ± 2.00	0.7 ± 0.76	-2.0 ± 99999	3.0 ± 2.83	99999 ± 99999	0.0 ± 99999	0.0 ± 0.00
Cycle 29 Day 1\|	99999 ± 99999	-1.5 ± 2.12	99999 ± 99999	0.5 ± 1.73	0.1 ± 1.81	0.0 ± 99999	3.5 ± 3.54	99999 ± 99999	0.0 ± 99999	0.0 ± 0.00
Cycle 30 Day 1\|	99999 ± 99999	0.0 ± 0.00	99999 ± 99999	0.8 ± 1.50	0.4 ± 0.55	0.0 ± 99999	3.0 ± 2.83	99999 ± 99999	0.0 ± 99999	-1.0 ± 1.00
Cycle 31 Day 1\|	99999 ± 99999	0.5 ± 0.71	99999 ± 99999	1.0 ± 2.65	0.7 ± 0.82	0.0 ± 99999	3.0 ± 4.24	99999 ± 99999	99999 ± 99999	0.0 ± 0.00
Cycle 32 Day 1\|	99999 ± 99999	0.0 ± 0.00	99999 ± 99999	1.3 ± 2.31	0.4 ± 0.55	99999 ± 99999	3.5 ± 3.54	99999 ± 99999	0.0 ± 99999	0.0 ± 0.00
Cycle 33 Day 1\|	99999 ± 99999	0.0 ± 0.00	99999 ± 99999	1.3 ± 2.31	0.5 ± 0.58	99999 ± 99999	3.5 ± 3.54	99999 ± 99999	0.0 ± 99999	0.0 ± 0.00
Cycle 34 Day 1\|	99999 ± 99999	0.0 ± 0.00	99999 ± 99999	0.0 ± 0.00	0.3 ± 0.50	99999 ± 99999	4.0 ± 4.24	99999 ± 99999	0.0 ± 99999	0.0 ± 0.00
Cycle 35 Day 1\|	99999 ± 99999	0.5 ± 0.71	99999 ± 99999	0.0 ± 99999	0.3 ± 0.50	99999 ± 99999	4.0 ± 4.24	99999 ± 99999	0.0 ± 99999	0.0 ± 99999
Cycle 36 Day 1\|	99999 ± 99999	-0.5 ± 0.71	99999 ± 99999	0.0 ± 99999	0.0 ± 0.00	99999 ± 99999	4.0 ± 4.24	99999 ± 99999	0.0 ± 99999	0.0 ± 99999
Cycle 37 Day 1\|	99999 ± 99999	0.0 ± 0.00	99999 ± 99999	-1.0 ± 99999	0.0 ± 0.00	99999 ± 99999	3.5 ± 4.95	99999 ± 99999	99999 ± 99999	99999 ± 99999
Cycle 38 Day 1\|	99999 ± 99999	0.0 ± 0.00	99999 ± 99999	0.0 ± 99999	0.0 ± 0.00	99999 ± 99999	3.0 ± 2.83	99999 ± 99999	0.0 ± 99999	99999 ± 99999
Cycle 39 Day 1\|	99999 ± 99999	0.0 ± 99999	99999 ± 99999	0.0 ± 99999	-0.5 ± 0.71	99999 ± 99999	3.5 ± 4.95	99999 ± 99999	99999 ± 99999	99999 ± 99999
Cycle 40 Day 1\|	99999 ± 99999	0.5 ± 0.71	99999 ± 99999	-1.0 ± 99999	0.0 ± 99999	99999 ± 99999	4.0 ± 4.24	99999 ± 99999	99999 ± 99999	99999 ± 99999
Cycle 41 Day 1\|	99999 ± 99999	0.5 ± 0.71	99999 ± 99999	0.0 ± 99999	0.0 ± 99999	99999 ± 99999	1.5 ± 6.36	99999 ± 99999	99999 ± 99999	99999 ± 99999
Cycle 42 Day 1\|	99999 ± 99999	-0.5 ± 0.71	99999 ± 99999	0.0 ± 99999	0.0 ± 99999	99999 ± 99999	4.0 ± 4.24	99999 ± 99999	99999 ± 99999	99999 ± 99999
Cycle 43 Day 1\|	99999 ± 99999	0.0 ± 0.00	99999 ± 99999	0.0 ± 99999	99999 ± 99999	99999 ± 99999	4.0 ± 4.24	99999 ± 99999	99999 ± 99999	99999 ± 99999
Cycle 44 Day 1\|	99999 ± 99999	1.0 ± 99999	99999 ± 99999	-1.0 ± 99999	99999 ± 99999	99999 ± 99999	3.0 ± 4.24	99999 ± 99999	99999 ± 99999	99999 ± 99999
Cycle 45 Day 1\|	99999 ± 99999	1.0 ± 99999	99999 ± 99999	0.0 ± 99999	99999 ± 99999	99999 ± 99999	1.0 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
Cycle 46 Day 1\|	99999 ± 99999	0.0 ± 99999	99999 ± 99999	-1.0 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
Cycle 47 Day 1\|	99999 ± 99999	0.0 ± 99999	99999 ± 99999	0.0 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
Cycle 48 Day 1\|	99999 ± 99999	-3.0 ± 99999	99999 ± 99999	0.0 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
Cycle 49 Day 1\|	99999 ± 99999	0.5 ± 0.71	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
Cycle 50 Day 1\|	99999 ± 99999	-3.0 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
Cycle 51 Day 1\|	99999 ± 99999	-0.5 ± 0.71	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
Cycle 52 Day 1\|	99999 ± 99999	1.0 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999	99999 ± 99999
End of treatment\|	-8.0 ± 99999	99999 ± 99999	0.7 ± 1.15	-2.0 ± 99999	-2.3 ± 5.19	99999 ± 99999	99999 ± 99999	99999 ± 99999	-15.0 ± 99999	0.0 ± 99999

Notes
[51] - Not all subjects had evaluable data at each time point.
[52] - Not all subjects had evaluable data at each time point.
[53] - Not all subjects had evaluable data at each time point.
[54] - Not all subjects had evaluable data at each time point.
[55] - Not all subjects had evaluable data at each time point.
[56] - Not all subjects had evaluable data at each time point.
[57] - Not all subjects had evaluable data at each time point.
[58] - Not all subjects had evaluable data at each time point.
[59] - Not all subjects had evaluable data at each time point.
[60] - Not all subjects had evaluable data at each time point.

No statistical analyses for this end point

Secondary: Time to Tumor Response (TTR) and Intracranial TTR (Phase 2)

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End point title

Time to Tumor Response (TTR) and Intracranial TTR (Phase 2) ^[61]

End point description

End point type

Secondary

End point timeframe

3 years

Notes
[61] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: All other reporting arms are not applicable to this end point.

End point values	EXP-1 (Phase 2)	EXP-2 (Phase 2)	EXP-3 (Phase 2)	EXP-4 (Phase 2)	EXP-5 (Phase 2)	EXP-6 (Phase 2)
Number of subjects analysed	27 ^[62]	20 ^[63]	30 ^[64]	27 ^[65]	16 ^[66]	17 ^[67]
Units: months
median (full range (min-max))
TTR\|	1.4 (1.2 to 5.4)	1.4 (1.2 to 11.0)	1.4 (1.1 to 5.7)	2.6 (1.2 to 9.9)	1.4 (1.2 to 4.0)	1.4 (1.3 to 4.2)
Intracranial TTR\|	2.1 (1.2 to 2.8)	1.4 (1.2 to 1.5)	1.4 (1.1 to 5.7)	1.5 (1.2 to 6.2)	1.4 (1.2 to 3.3)	1.4 (1.2 to 5.5)

Notes
[62] - Number of subjects analyzed for intracranial TTR is 6.
[63] - Number of subjects analyzed for intracranial TTR is 10.
[64] - Number of subjects analyzed for intracranial TTR is 20.
[65] - Number of subjects analyzed for intracranial TTR is 25.
[66] - Number of subjects analyzed for intracranial TTR is 15.
[67] - Number of subjects analyzed for intracranial TTR is 14.

No statistical analyses for this end point

Secondary: Duration of Response (DOR) and Intracranial DOR (Phase 2)

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End point title

Duration of Response (DOR) and Intracranial DOR (Phase 2) ^[68]

End point description

Duration of Response (DOR) was 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 occurred first. DOR was only calculated for the subgroup of subjects with a confirmed objective tumor response. Intracranial DOR was only calculated for subjects with confirmed intracranial objective response. Results presented here were based on independent central review. "99999" and "-99999" represent "not applicable" or "non evaluable" data.

End point type

Secondary

End point timeframe

3 years

Notes
[68] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: All other reporting arms are not applicable to this end point.

End point values	EXP-1 (Phase 2)	EXP-2 (Phase 2)	EXP-3 (Phase 2)	EXP-4 (Phase 2)	EXP-5 (Phase 2)	EXP-6 (Phase 2)
Number of subjects analysed	27 ^[69]	20 ^[70]	30 ^[71]	27 ^[72]	16 ^[73]	17 ^[74]
Units: months
median (confidence interval 95%)
DOR\|	99999 (10.02 to 99999)	99999 (99999 to 99999)	99999 (6.80 to 99999)	6.93 (5.22 to 99999)	99999 (4.17 to 99999)	13.83 (11.10 to 99999)
Intra-cranial DOR\|	9.15 (8.28 to 10.02)	99999 (99999 to 99999)	99999 (8.38 to 99999)	14.52 (-99999 to 99999)	8.31 (6.93 to 99999)	99999 (4.99 to 99999)

Notes
[69] - Number of subjects analyzed for intracranial DOR is 6.
[70] - Number of subjects analyzed for intracranial DOR is 10.
[71] - Number of subjects analyzed for intracranial DOR is 20.
[72] - Number of subjects analyzed for intracranial DOR is 25.
[73] - Number of subjects analyzed for intracranial DOR is 15.
[74] - Number of subjects analyzed for intracranial DOR is 14.

No statistical analyses for this end point

Secondary: Percentage of Subjects Achieving Disease Control and Intracranial Disease Control at 12 Weeks (Phase 2)

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End point title

Percentage of Subjects Achieving Disease Control and Intracranial Disease Control at 12 Weeks (Phase 2) ^[75]

End point description

Tumor response was evaluated according to RECIST version 1.1, and disease control was defined as confirmed complete response (CR), confirmed partial response (PR), or stable disease (SD). Intracranial assessment was only performed for subjects with CNS metastases. Results presented here were based on independent central review.

End point type

Secondary

End point timeframe

12 weeks

Notes
[75] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: All other reporting arms are not applicable to this end point.

End point values	EXP-1 (Phase 2)	EXP-2 (Phase 2)	EXP-3 (Phase 2)	EXP-4 (Phase 2)	EXP-5 (Phase 2)	EXP-6 (Phase 2)
Number of subjects analysed	30 ^[76]	27 ^[77]	59 ^[78]	65 ^[79]	46 ^[80]	47 ^[81]
Units: percentage of subjects
number (confidence interval 95%)
Disease control rate\|	93.3 (77.9 to 99.2)	85.2 (66.3 to 95.8)	67.8 (54.4 to 79.4)	63.1 (50.2 to 74.7)	52.2 (36.9 to 67.1)	63.8 (48.5 to 77.3)
Intra-cranial disease control rate\|	87.5 (47.3 to 99.7)	94.1 (71.3 to 99.9)	75.0 (56.6 to 88.5)	77.8 (62.9 to 88.8)	68.4 (51.3 to 82.5)	72.0 (50.6 to 87.9)

Notes
[76] - Number of subjects analyzed for intracranial disease control is 8.
[77] - Number of subjects analyzed for intracranial disease control is 17.
[78] - Number of subjects analyzed for intracranial disease control is 32.
[79] - Number of subjects analyzed for intracranial disease control is 45.
[80] - Number of subjects analyzed for intracranial disease control is 38.
[81] - Number of subjects analyzed for intracranial disease control is 25.

No statistical analyses for this end point

Secondary: Time to Progression (TTP) on the Last Prior Therapy (Phase 2)

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End point title

Time to Progression (TTP) on the Last Prior Therapy (Phase 2) ^[82]

End point description

TTP on the last prior therapy was defined as time from the first dose date of the last prior treatment regimen to the date of progression.

End point type

Secondary

End point timeframe

3 years

Notes
[82] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: All other reporting arms are not applicable to this end point.

End point values	EXP-2 (Phase 2)	EXP-3 (Phase 2)	EXP-4 (Phase 2)	EXP-5 (Phase 2)
Number of subjects analysed	27	59	65	46
Units: months
median (confidence interval 95%)
Prior systemic therapy before PF-06463922\|	11.5 (7.2 to 19.6)	12.8 (9.2 to 16.9)	10.2 (7.6 to 14.9)	3.7 (2.1 to 6.4)
Prior ALK+/ROS1+ TKI treatment\|	11.5 (7.2 to 19.6)	12.9 (11.2 to 18.1)	12.1 (7.9 to 16.4)	3.7 (2.1 to 6.6)
Prior systemic therapy other than ALK+/ROS1+ TKI\|	19.6 (16.1 to 30.7)	8.5 (5.0 to 12.6)	5.0 (3.1 to 10.8)	5.6 (4.7 to 11.2)

No statistical analyses for this end point

Secondary: Time to Tumor Progression (Phase 2)

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End point title

Time to Tumor Progression (Phase 2) ^[83]

End point description

Time to progression (TTP) was defined as the time from the first dose of study treatment to the first documentation of objective disease progression. Intracranial TTP was defined as the time from the first dose of study treatment to the date of the first documentation of objective progression of intracranial disease, based on either new brain metastases or progression of existing brain metastases. Results presented here were based on independent central review. ITT analysis set was used for TTP determination and included all enrolled subjects with documented ALK or ROS1 rearrangement who received at least 1 dose of PF-06463922; ITT subjects with CNS metastases were analyzed for intracranial TTP. "99999" represents "not applicable" or "non evaluable" data.

End point type

Secondary

End point timeframe

3 years

Notes
[83] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: All other reporting arms are not applicable to this end point.

End point values	EXP-1 (Phase 2)	EXP-2 (Phase 2)	EXP-3 (Phase 2)	EXP-4 (Phase 2)	EXP-5 (Phase 2)	EXP-6 (Phase 2)
Number of subjects analysed	30 ^[84]	27 ^[85]	59 ^[86]	65 ^[87]	46 ^[88]	47 ^[89]
Units: months
median (confidence interval 95%)
TTP\|	99999 (11.4 to 99999)	99999 (99999 to 99999)	9.0 (5.5 to 99999)	8.4 (5.6 to 13.7)	7.1 (4.1 to 12.5)	12.5 (8.2 to 99999)
Intracranial\|	11.4 (9.6 to 11.4)	99999 (99999 to 99999)	99999 (6.9 to 99999)	15.7 (11.0 to 15.7)	99999 (8.3 to 99999)	99999 (99999 to 99999)

Notes
[84] - Number of subjects analyzed for intracranial TTP is 8.
[85] - Number of subjects analyzed for intracranial TTP is 17.
[86] - Number of subjects analyzed for intracranial TTP is 32.
[87] - Number of subjects analyzed for intracranial TTP is 45.
[88] - Number of subjects analyzed for intracranial TTP is 38.
[89] - Number of subjects analyzed for intracranial TTP is 25.

No statistical analyses for this end point

Secondary: Probability of First Event Being a Central Nervous System (CNS) Progression, Non CNS Progression, or Death (Phase 2)

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End point title

Probability of First Event Being a Central Nervous System (CNS) Progression, Non CNS Progression, or Death (Phase 2)

End point description

End point type

Secondary

End point timeframe

3 years

End point values	Phase 2 ITT Population
Number of subjects analysed	274
Units: not applicable
number (not applicable)
CNS progression	0.179
Non CNS progression	0.325
Death	0.055

No statistical analyses for this end point

Secondary: Progression-Free Survival (PFS) (Phase 2)

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End point title

Progression-Free Survival (PFS) (Phase 2) ^[90]

End point description

End point type

Secondary

End point timeframe

3 years

Notes
[90] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: All other reporting arms are not applicable to this end point.

End point values	EXP-1 (Phase 2)	EXP-2 (Phase 2)	EXP-3 (Phase 2)	EXP-4 (Phase 2)	EXP-5 (Phase 2)	EXP-6 (Phase 2)
Number of subjects analysed	30 ^[91]	27 ^[92]	59 ^[93]	65 ^[94]	46 ^[95]	47 ^[96]
Units: months
median (confidence interval 95%)	99999 (11.4 to 99999)	99999 (99999 to 99999)	8.2 (5.5 to 99999)	7.3 (5.4 to 11.0)	5.6 (4.0 to 12.5)	9.6 (4.7 to 99999)

Notes
[91] - Number of subjects with objective progression or death is 7; others were censored.
[92] - Number of subjects with objective progression or death is 8; others were censored.
[93] - Number of subjects with objective progression or death is 30; others were censored.
[94] - Number of subjects with objective progression or death is 36; others were censored.
[95] - Number of subjects with objective progression or death is 26; others were censored.
[96] - Number of subjects with objective progression or death is 21; others were censored.

No statistical analyses for this end point

Secondary: Overall Survival (Phase 2)

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End point title

Overall Survival (Phase 2) ^[97]

End point description

OS was defined as the time from first dose to the date of death due to any cause. For subjects still alive at the time of analysis, the OS time was censored on the last date the subjects were known to be alive. Estimates of OS and its 95% confidence interval were determined using Kaplan-Meier method. ITT set was used for OS analysis, and it included all enrolled subjects with documented ALK or ROS1 rearrangement who received at least 1 dose of PF-06463922. "99999" represents "not applicable" or "non evaluable" data.

End point type

Secondary

End point timeframe

3 years

Notes
[97] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: All other reporting arms are not applicable to this end point.

End point values	EXP-1 (Phase 2)	EXP-2 (Phase 2)	EXP-3 (Phase 2)	EXP-4 (Phase 2)	EXP-5 (Phase 2)	EXP-6 (Phase 2)
Number of subjects analysed	30 ^[98]	27 ^[99]	59 ^[100]	65 ^[101]	46 ^[102]	47 ^[103]
Units: months
median (confidence interval 95%)	99999 (99999 to 99999)	99999 (12.1 to 99999)	99999 (14.4 to 99999)	99999 (14.7 to 99999)	99999 (9.7 to 99999)	99999 (99999 to 99999)

Notes
[98] - Number of death is 1; others were censored.
[99] - Number of death is 4; others were censored.
[100] - Number of death is 14; others were censored.
[101] - Number of death is 20; others were censored.
[102] - Number of death is 15; others were censored.
[103] - Number of death is 10; others were censored.

No statistical analyses for this end point

Secondary: Maximum Observed Plasma Concentration (Cmax) of PF-06463922 (Phase 2)

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End point title

Maximum Observed Plasma Concentration (Cmax) of PF-06463922 (Phase 2)

End point description

Maximum observed plasma concentration (Cmax) of PF-06463922 was observed directly from data. PK concentration analysis set of PF-06463922 included all subjects treated who had at least 1 concentration of PF-06463922.

End point type

Secondary

End point timeframe

Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24, 48, 72, 96 and 120 hours post-dose on Day -7 and pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 15

End point values	Phase 2 and Japan LIC PK Analysis Set
Number of subjects analysed	22 ^[104]
Units: ng/mL
geometric mean (geometric coefficient of variation)
Day -7\|	695.2 ± 40
Cycle 1 Day 15\|	576.5 ± 42

Notes
[104] - Number of subjects contributing to Day -7 data is 19.

No statistical analyses for this end point

Secondary: Time for Cmax (Tmax) of PF-06463922 (Phase 2)

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End point title

Time for Cmax (Tmax) of PF-06463922 (Phase 2)

End point description

End point type

Secondary

End point timeframe

Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24, 48, 72, 96 and 120 hours post-dose on Day -7 and pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 15

End point values	Phase 2 and Japan LIC PK Analysis Set
Number of subjects analysed	22 ^[105]
Units: hours
median (full range (min-max))
Day -7\|	1.15 (0.50 to 4.02)
Cycle 1 Day 15\|	1.96 (0.50 to 22.7)

Notes
[105] - Number of subjects contributing to Day -7 data is 19.

No statistical analyses for this end point

Secondary: Area under the Plasma Concentration-Time Profile from Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06463922 (Phase 2)

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End point title

Area under the Plasma Concentration-Time Profile from Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06463922 (Phase 2)

End point description

End point type

Secondary

End point timeframe

Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24, 48, 72, 96 and 120 hours post-dose on Day -7

End point values	Phase 2 and Japan LIC PK Analysis Set
Number of subjects analysed	16
Units: ng*hour/mL
geometric mean (geometric coefficient of variation)	9088 ± 35

No statistical analyses for this end point

Secondary: Area under the Plasma Concentration-Time profile from Time Zero to Time Tau (AUCtau) of PF-06463922 (Phase 2)

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End point title

Area under the Plasma Concentration-Time profile from Time Zero to Time Tau (AUCtau) of PF-06463922 (Phase 2)

End point description

Tau refers to the dosing interval, and it equals to 24 hours for QD dosing which was adopted in Phase 2. AUCtau was determined using linear/log trapezoidal method. PK parameter analysis set for PF-06463922 included all enrolled subjects who received at least 1 dose of PF-06463922 and had sufficient information to estimate at least one of the PK parameters of interest for PF-06463922.

End point type

Secondary

End point timeframe

Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post-dose on Day -7 and pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 15

End point values	Phase 2 and Japan LIC PK Analysis Set
Number of subjects analysed	22 ^[106]
Units: ng*hour/mL
geometric mean (geometric coefficient of variation)
Day -7\|	5308 ± 36
Cycle 1 Day 15\|	5650 ± 39

Notes
[106] - Number of subjects contributing to Day -7 data is 19.

No statistical analyses for this end point

Secondary: Apparent Oral Clearance (CL/F) of PF-06463922 (Phase 2)

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End point title

Apparent Oral Clearance (CL/F) of PF-06463922 (Phase 2)

End point description

End point type

Secondary

End point timeframe

Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24, 48, 72, 96 and 120 hours post-dose on Day -7 and pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 15

End point values	Phase 2 and Japan LIC PK Analysis Set
Number of subjects analysed	22 ^[107]
Units: liter/hour
geometric mean (geometric coefficient of variation)
Day -7\|	11.01 ± 35
Cycle 1 Day 15\|	17.70 ± 39

Notes
[107] - Number of subjects contributing to Day -7 data is 16.

No statistical analyses for this end point

Secondary: Apparent Volume of Distribution (Vz/F) of PF-06463922 (Phase 2)

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End point title

Apparent Volume of Distribution (Vz/F) of PF-06463922 (Phase 2)

End point description

End point type

Secondary

End point timeframe

Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24, 48, 72, 96 and 120 hours post-dose on Day -7

End point values	Phase 2 and Japan LIC PK Analysis Set
Number of subjects analysed	16
Units: liters
geometric mean (geometric coefficient of variation)	351.5 ± 37

No statistical analyses for this end point

Secondary: Terminal Half-Life of PF-06463922 (Phase 2)

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End point title

Terminal Half-Life of PF-06463922 (Phase 2)

End point description

Terminal plasma half-life was defined as the time measured for the plasma concentration to decrease by one half, and calculated as loge(2)/kel, where kel was the rate constant for terminal phase. PK parameter analysis set for PF-06463922 included all enrolled subjects who received at least 1 dose of PF-06463922 and had sufficient information to estimate at least one of the PK parameters of interest for PF-06463922.

End point type

Secondary

End point timeframe

Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, 24, 48, 72, 96 and 120 hours post-dose on Day -7

End point values	Phase 2 and Japan LIC PK Analysis Set
Number of subjects analysed	16
Units: hours
arithmetic mean (standard deviation)	23.58 ± 9.3743

No statistical analyses for this end point

Secondary: Observed Accumulation Ratio (Rac) of PF-06463922 Following Multiple Oral Doses (Phase 2)

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End point title

Observed Accumulation Ratio (Rac) of PF-06463922 Following Multiple Oral Doses (Phase 2)

End point description

Rac was calculated as Day 15 AUCtau/Day -7 AUCtau, where AUCtau was the area under the plasma concentration-time profile from time 0 to time tau (24 hours for QD dosing regimen which was adopted in Phase 2). PK parameter analysis set for PF-06463922 included all enrolled subjects who received at least 1 dose of PF-06463922 and had sufficient information to estimate at least one of the PK parameters of interest for PF-06463922.

End point type

Secondary

End point timeframe

Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 15

End point values	Phase 2 and Japan LIC PK Analysis Set
Number of subjects analysed	20
Units: ratio
arithmetic mean (standard deviation)	1.082 ± 0.42701

No statistical analyses for this end point

Secondary: Steady State Accumulation Ratio (Rss) of PF-06463922 Following Multiple Oral Doses (Phase 2)

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End point title

Steady State Accumulation Ratio (Rss) of PF-06463922 Following Multiple Oral Doses (Phase 2)

End point description

Rss was calculated as Day 15 AUCtau/Day -7 AUCinf, where AUCtau was the area under the plasma concentration-time profile from time 0 to time tau (24 hours for QD dosing regimen which was adopted in Phase 2), and AUCinf was the area under the plasma concentration-time profile from time 0 extrapolated to infinite time. PK parameter analysis set for PF-06463922 included all enrolled subjects who received at least 1 dose of PF-06463922 and had sufficient information to estimate at least one of the PK parameters of interest for PF- 06463922.

End point type

Secondary

End point timeframe

Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9 and 24 hours post-dose on Cycle 1 Day 15

End point values	Phase 2 and Japan LIC PK Analysis Set
Number of subjects analysed	14
Units: ratio
arithmetic mean (standard deviation)	0.6577 ± 0.28627

No statistical analyses for this end point

Secondary: Number of Subjects with ALK Mutation Based on Plasma CNA Analysis (Phase 2)

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End point title

Number of Subjects with ALK Mutation Based on Plasma CNA Analysis (Phase 2) ^[108]

End point description

Plasma CNA samples were analyzed for ALK kinase domain mutations by Next Generation Sequencing (NGS). Number of subjects with one or more ALK mutations is presented. CNA peripheral blood analysis set included all subjects of the ITT analysis set who had at least 1 molecular biomarker assayed.

End point type

Secondary

End point timeframe

Screening

Notes
[108] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: All other reporting arms are not applicable to this end point.

End point values	EXP-1 (Phase 2)	EXP-2 (Phase 2)	EXP-3 (Phase 2)	EXP-4 (Phase 2)	EXP-5 (Phase 2)
Number of subjects analysed	30	26	58	61	45
Units: subjects	1	6	8	17	14

No statistical analyses for this end point

Secondary: Number of Subjects with ALK Mutation Based on Tumor Tissue Analysis (Phase 2)

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End point title

Number of Subjects with ALK Mutation Based on Tumor Tissue Analysis (Phase 2) ^[109]

End point description

End point type

Secondary

End point timeframe

Screening

Notes
[109] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: All other reporting arms are not applicable to this end point.

End point values	EXP-1 (Phase 2)	EXP-2 (Phase 2)	EXP-3 (Phase 2)	EXP-4 (Phase 2)	EXP-5 (Phase 2)
Number of subjects analysed	26	26	52	48	33
Units: subjects	0	7	8	11	13

No statistical analyses for this end point

Secondary: Number of Subjects Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2)

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End point title

Number of Subjects Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 2) ^[110]

End point description

End point type

Secondary

End point timeframe

3 years

Notes
[110] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: All other reporting arms are not applicable to this end point.

End point values	EXP-1 (Phase 2)	EXP-2 (Phase 2)	EXP-3 (Phase 2)	EXP-4 (Phase 2)	EXP-5 (Phase 2)	EXP-6 (Phase 2)
Number of subjects analysed	30	26	55	60	43	40 ^[111]
Units: subjects
Improved in global QoL\|	17	11	18	25	18	20
Stable in global QoL\|	10	13	26	22	17	13
Worsened in global QoL\|	3	2	11	13	8	7
Improved in physical functioning\|	10	7	14	23	8	11
Stable in physical functioning\|	14	19	37	27	25	24
Worsened in physical functioning\|	6	0	4	10	10	5
Improved in role functioning\|	12	8	18	25	16	17
Stable in role functioning\|	11	15	31	19	16	19
Worsened in role functioning\|	7	3	6	16	11	3
Improved in emotional functioning\|	12	12	18	21	18	17
Stable in emotional functioning\|	14	14	29	32	20	20
Worsened in emotional functioning\|	4	0	8	7	5	3
Improved in cognitive functioning\|	10	3	11	13	13	12
Stable in cognitive functioning\|	12	15	31	35	16	22
Worsened in cognitive functioning\|	8	8	13	12	14	6
Improved in social functioning\|	14	7	18	22	12	13
Stable in social functioning\|	13	17	32	28	23	22
Worsened in social functioning\|	3	2	5	10	8	5
Improved in fatigue\|	17	14	22	29	26	17
Stable in fatigue\|	9	11	25	22	11	19
Worsened in fatigue\|	4	1	8	9	6	4
Improved in nausea and vomiting\|	8	4	11	16	14	10
Stable in nausea and vomiting\|	22	22	43	38	28	28
Worsened in nausea and vomiting\|	0	0	1	6	1	2
Improved in pain\|	14	9	19	23	18	21
Stable in pain\|	11	15	27	26	20	12
Worsened in pain\|	5	2	9	11	5	7
Improved in dyspnea\|	15	9	10	21	14	13
Stable in dyspnea\|	11	14	34	22	21	19
Worsened in dyspnea\|	4	3	11	17	8	8
Improved in insomnia\|	19	8	19	28	22	19
Stable in insomnia\|	10	14	28	23	14	18
Worsened in insomnia\|	1	4	8	9	7	3
Improved in appetite loss\|	14	4	17	29	22	20
Stable in appetite loss\|	16	22	37	26	21	20
Worsened in appetite loss\|	0	0	1	5	0	0
Improved in constipation\|	10	6	9	15	11	13
Stable in constipation\|	13	18	36	33	28	23
Worsened in constipation\|	7	2	10	12	4	4
Improved in diarrhea\|	5	3	8	9	11	8
Stable in diarrhea\|	19	22	42	40	26	28
Worsened in diarrhea\|	6	1	5	11	6	4
Improved in financial difficulties\|	10	6	11	13	11	10
Stable in financial difficulties\|	18	18	33	38	22	26
Worsened in financial difficulties\|	2	2	11	9	10	4

Notes
[111] - Number of subjects analyzed for role functioning is 39.

No statistical analyses for this end point

Secondary: Number of Subjects Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2)

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End point title

Number of Subjects Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 2) ^[112]

End point description

End point type

Secondary

End point timeframe

3 years

Notes
[112] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: All other reporting arms are not applicable to this end point.

End point values	EXP-1 (Phase 2)	EXP-2 (Phase 2)	EXP-3 (Phase 2)	EXP-4 (Phase 2)	EXP-5 (Phase 2)	EXP-6 (Phase 2)
Number of subjects analysed	30	26	55 ^[113]	60	42	41
Units: subjects
Improved in dyspnea\|	11	5	11	20	12	13
Stable in dyspnea\|	16	19	36	26	22	22
Worsened in dyspnea\|	3	2	8	14	8	6
Improved in coughing\|	18	9	22	27	18	17
Stable in coughing\|	9	14	26	27	15	17
Worsened in coughing\|	3	3	7	6	9	7
Improved in hemoptysis\|	4	0	7	5	5	4
Stable in hemoptysis\|	24	26	47	53	34	36
Worsened in hemoptysis\|	2	0	1	2	3	1
Improved in sore mouth\|	0	2	4	10	2	5
Stable in sore mouth\|	24	21	45	39	32	28
Worsened in sore mouth\|	6	3	6	11	8	8
Improved in dysphagia\|	3	1	5	7	4	5
Stable in dysphagia\|	24	25	44	47	33	30
Worsened in dysphagia\|	3	0	6	6	5	6
Improved in peripheral neuropathy\|	2	4	9	5	6	8
Stable in peripheral neuropathy\|	10	13	25	32	23	19
Worsened in peripheral neuropathy\|	18	9	21	23	13	14
Improved in alopecia\|	1	1	2	10	8	9
Stable in alopecia\|	19	22	41	38	27	26
Worsened in alopecia\|	10	3	12	12	7	6
Improved in chest pain\|	11	5	14	18	14	14
Stable in chest pain\|	15	19	36	33	25	22
Worsened in chest pain\|	4	2	4	9	3	5
Improved in arm or shoulder pain\|	9	4	13	14	12	12
Stable in arm or shoulder pain\|	16	18	33	37	21	21
Worsened in arm or shoulder pain\|	5	4	9	9	9	8
Improved in pain in other parts\|	10	5	18	19	14	17
Stable in pain in other parts\|	14	12	23	25	11	17
Worsened in pain in other parts\|	6	9	14	16	16	7

Notes
[113] - Number of subjects analyzed for chest pain is 54.

No statistical analyses for this end point

Secondary: Number of Subjects with Treatment-Emergent Adverse Events (Phase 1 and Phase 2)

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End point title

Number of Subjects with Treatment-Emergent Adverse Events (Phase 1 and Phase 2) ^[114]

End point description

AE was any untoward medical occurrence in a clinical investigation subject administered a product or medical device, regardless of the causal relationship to study treatment. Treatment-emergent AEs (TEAEs) were AEs which occurred for the first time during the effective duration of treatment or AEs that increased in severity during treatment. Serious AEs (SAEs) were any untoward medical occurrence at any dose that resulted in death; was life-threatening; required inpatient hospitalization or caused prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity. AEs included SAEs and non-serious AEs. Causality to study treatment was determined by the investigator. Severity was graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03. The safety analysis set included all enrolled subjects who received at least 1 dose of PF-06463922.

End point type

Secondary

End point timeframe

3 years

Notes
[114] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: All other reporting arms are not applicable to this end point.

End point values	10 mg QD (Phase 1)	25 mg QD (Phase 1)	50 mg QD (Phase 1)	75 mg QD (Phase 1)	100 mg QD (Phase 1)	150 mg QD (Phase 1)	200 mg QD (Phase 1)	35 mg BID (Phase 1)	75 mg BID (Phase 1)	100 mg BID (Phase 1)	EXP-1 (Phase 2)	EXP-2 (Phase 2)	EXP-3 (Phase 2)	EXP-4 (Phase 2)	EXP-5 (Phase 2)	EXP-6 (Phase 2)
Number of subjects analysed	3	3	3	12	17	3	3	3	3	4	30	27	60	65	46	47
Units: subjects
AEs (all causality)\|	3	3	3	12	17	3	3	3	3	4	30	27	59	65	46	47
AEs (treatment-related)\|	3	3	3	11	16	3	3	1	3	4	30	27	55	61	43	45
SAEs (all causality)\|	3	1	1	4	9	3	1	2	2	2	8	5	18	24	18	16
SAEs (treatment-related)\|	1	0	0	1	1	3	0	0	0	1	3	0	5	4	5	2
Grade 1 (all causality)\|	0	0	1	1	0	0	0	0	0	0	3	0	5	3	3	0
Grade 2 (all causality)\|	0	1	2	4	5	0	1	1	1	0	12	11	20	19	11	12
Grade 3 (all causality)\|	2	0	0	5	8	0	2	1	0	1	12	12	24	28	20	26
Grade 4 (all causality)\|	0	1	0	1	1	1	0	1	1	3	3	3	3	7	4	3
Grade 5 (all causality)\|	1	1	0	1	3	2	0	0	1	0	0	1	7	8	8	6

No statistical analyses for this end point

Secondary: Number of Subjects with Laboratory Abnormalities (Phase 1 and Phase 2) – Hematology

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End point title

Number of Subjects with Laboratory Abnormalities (Phase 1 and Phase 2) – Hematology ^[115]

End point description

Hematology evaluation included hemoglobin, platelets, white blood cell, absolute neutrophils, absolute lymphocytes, absolute monocytes, absolute eosinophils and absolute basophils. The safety analysis set included all enrolled subjects who received at least 1 dose of PF-06463922.

End point type

Secondary

End point timeframe

3 years

Notes
[115] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: All other reporting arms are not applicable to this end point.

End point values	10 mg QD (Phase 1)	25 mg QD (Phase 1)	50 mg QD (Phase 1)	75 mg QD (Phase 1)	100 mg QD (Phase 1)	150 mg QD (Phase 1)	200 mg QD (Phase 1)	35 mg BID (Phase 1)	75 mg BID (Phase 1)	100 mg BID (Phase 1)	EXP-1 (Phase 2)	EXP-2 (Phase 2)	EXP-3 (Phase 2)	EXP-4 (Phase 2)	EXP-5 (Phase 2)	EXP-6 (Phase 2)
Number of subjects analysed	3 ^[116]	3 ^[117]	3 ^[118]	12 ^[119]	17 ^[120]	3 ^[121]	3 ^[122]	3 ^[123]	3 ^[124]	4 ^[125]	30 ^[126]	27 ^[127]	60 ^[128]	64 ^[129]	45 ^[130]	47 ^[131]
Units: subjects
Anemia\|	3	3	3	8	16	3	3	3	3	4	20	14	50	48	35	32
Hemoglobin increased\|	0	0	0	0	0	0	0	0	0	0	0	0	1	3	1	1
Lymphocyte count decreased\|	2	2	2	6	4	3	3	0	0	2	9	9	21	29	18	21
Lymphocyte count increased\|	1	0	0	0	3	1	0	0	0	0	3	3	6	4	2	1
Neutrophil count decreased\|	1	0	0	4	2	0	0	0	0	1	5	2	7	6	1	5
Platelet count decreased\|	2	2	0	4	5	1	0	0	0	1	6	9	13	9	10	11
White blood cell decreased\|	2	0	0	4	2	2	1	0	0	1	6	3	6	9	5	8

Notes
[116] - Not all subjects had evaluable data for each parameter.
[117] - Not all subjects had evaluable data for each parameter.
[118] - Not all subjects had evaluable data for each parameter.
[119] - Not all subjects had evaluable data for each parameter.
[120] - Not all subjects had evaluable data for each parameter.
[121] - Not all subjects had evaluable data for each parameter.
[122] - Not all subjects had evaluable data for each parameter.
[123] - Not all subjects had evaluable data for each parameter.
[124] - Not all subjects had evaluable data for each parameter.
[125] - Not all subjects had evaluable data for each parameter.
[126] - Not all subjects had evaluable data for each parameter.
[127] - Not all subjects had evaluable data for each parameter.
[128] - Not all subjects had evaluable data for each parameter.
[129] - Not all subjects had evaluable data for each parameter.
[130] - Not all subjects had evaluable data for each parameter.
[131] - Not all subjects had evaluable data for each parameter.

No statistical analyses for this end point

Secondary: Number of Subjects with Laboratory Abnormalities (Phase 1 and Phase 2) – Chemistry

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End point title

Number of Subjects with Laboratory Abnormalities (Phase 1 and Phase 2) – Chemistry ^[132]

End point description

Chemistry evaluation included alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, sodium, potassium, magnesium, chloride, total calcium, total bilirubin, blood urea nitrogen (BUN) or urea, creatinine, uric acid, glucose (non-fasted), albumin, phosphorus or phosphate, serum total amylase and serum lipase. The safety analysis set included all enrolled subjects who received at least 1 dose of PF-06463922.

End point type

Secondary

End point timeframe

3 years

Notes
[132] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: All other reporting arms are not applicable to this end point.

End point values	10 mg QD (Phase 1)	25 mg QD (Phase 1)	50 mg QD (Phase 1)	75 mg QD (Phase 1)	100 mg QD (Phase 1)	150 mg QD (Phase 1)	200 mg QD (Phase 1)	35 mg BID (Phase 1)	75 mg BID (Phase 1)	100 mg BID (Phase 1)	EXP-1 (Phase 2)	EXP-2 (Phase 2)	EXP-3 (Phase 2)	EXP-4 (Phase 2)	EXP-5 (Phase 2)	EXP-6 (Phase 2)
Number of subjects analysed	3 ^[133]	3 ^[134]	3 ^[135]	12 ^[136]	17 ^[137]	3 ^[138]	3 ^[139]	3 ^[140]	3 ^[141]	4 ^[142]	30 ^[143]	27 ^[144]	60 ^[145]	64 ^[146]	45 ^[147]	47 ^[148]
Units: subjects
ALT increased\|	2	1	1	4	7	2	2	0	0	3	11	11	23	17	12	13
Alkaline phosphatase increased\|	1	1	3	4	9	3	1	0	2	3	6	8	21	21	21	14
AST increased\|	2	2	2	3	7	2	2	0	1	3	15	12	31	27	17	17
Blood bilirubin increased\|	1	0	0	1	0	0	0	0	0	1	0	0	2	0	1	1
CPK increased\|	0	0	0	0	1	1	0	0	1	0	0	0	3	0	0	2
Creatinine increased\|	3	2	3	9	13	3	3	2	2	3	26	21	37	44	32	34
GGT increased\|	0	0	0	0	1	0	1	0	0	2	0	1	2	1	0	1
Hypercalcemia\|	0	0	0	0	1	1	0	0	0	1	4	3	4	4	3	1
Hyperglycemia\|	3	2	2	6	8	2	1	1	2	0	11	16	30	41	31	29
Hyperkalemia\|	0	1	2	2	6	1	1	1	1	2	8	7	14	11	5	5
Hypermagnesemia\|	2	0	0	1	2	0	0	0	0	0	2	1	2	2	1	3
Hypernatremia\|	0	1	0	0	4	2	0	0	0	1	3	1	2	4	2	4
Hypoalbuminemia\|	2	1	3	4	6	3	1	1	3	1	16	15	34	42	29	27
Hypocalcemia\|	1	0	1	3	3	2	1	0	0	1	2	4	11	9	3	9
Hypoglycemia\|	0	0	1	3	4	0	1	0	1	0	1	2	8	7	5	3
Hypokalemia\|	0	0	2	3	3	3	1	1	0	2	6	1	9	9	6	13
Hypomagnesemia\|	0	1	2	4	1	3	0	1	1	3	4	8	20	17	13	11
Hyponatremia\|	2	1	1	1	4	1	1	0	2	2	8	6	10	19	9	6
Hypophosphatemia\|	1	2	0	3	3	2	1	1	2	1	3	6	17	14	7	14
Lipase increased\|	3	1	0	8	6	0	1	0	2	2	9	5	11	15	14	16
Serum amylase increased\|	3	0	0	2	5	0	1	0	0	2	9	5	14	18	10	13

Notes
[133] - Not all subjects had evaluable data for each parameter.
[134] - Not all subjects had evaluable data for each parameter.
[135] - Not all subjects had evaluable data for each parameter.
[136] - Not all subjects had evaluable data for each parameter.
[137] - Not all subjects had evaluable data for each parameter.
[138] - Not all subjects had evaluable data for each parameter.
[139] - Not all subjects had evaluable data for each parameter.
[140] - Not all subjects had evaluable data for each parameter.
[141] - Not all subjects had evaluable data for each parameter.
[142] - Not all subjects had evaluable data for each parameter.
[143] - Not all subjects had evaluable data for each parameter.
[144] - Not all subjects had evaluable data for each parameter.
[145] - Not all subjects had evaluable data for each parameter.
[146] - Not all subjects had evaluable data for each parameter.
[147] - Not all subjects had evaluable data for each parameter.
[148] - Not all subjects had evaluable data for each parameter.

No statistical analyses for this end point

Secondary: Number of Subjects with Laboratory Abnormalities (Phase 1 and Phase 2) – Coagulation, Lipids and Urinalysis

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End point title

Number of Subjects with Laboratory Abnormalities (Phase 1 and Phase 2) – Coagulation, Lipids and Urinalysis ^[149]

End point description

Coagulation evaluation included activated partial thromboplastin time, international normalized ratio (INR), and prothrombin time. Lipid evaluation included total cholesterol, low density lipoprotein (LDL), high density lipoprotein (HDL) and triglycerides. Urinalysis included urine protein and urine blood. The safety analysis set included all enrolled subjects who received at least 1 dose of PF-06463922.

End point type

Secondary

End point timeframe

3 years

Notes
[149] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: All other reporting arms are not applicable to this end point.

End point values	10 mg QD (Phase 1)	25 mg QD (Phase 1)	50 mg QD (Phase 1)	75 mg QD (Phase 1)	100 mg QD (Phase 1)	150 mg QD (Phase 1)	200 mg QD (Phase 1)	35 mg BID (Phase 1)	75 mg BID (Phase 1)	100 mg BID (Phase 1)	EXP-1 (Phase 2)	EXP-2 (Phase 2)	EXP-3 (Phase 2)	EXP-4 (Phase 2)	EXP-5 (Phase 2)	EXP-6 (Phase 2)
Number of subjects analysed	3 ^[150]	3 ^[151]	3 ^[152]	12 ^[153]	17 ^[154]	3 ^[155]	3 ^[156]	3 ^[157]	3 ^[158]	4 ^[159]	30 ^[160]	27 ^[161]	60 ^[162]	65 ^[163]	46 ^[164]	47 ^[165]
Units: subjects
Activated partial thromboplastin time prolonged\|	1	0	1	3	2	0	0	0	0	0	1	0	1	0	1	4
Cholesterol high\|	2	2	2	10	16	2	3	3	2	3	30	26	57	64	45	44
Hypertriglyceridemia\|	0	2	2	10	16	2	3	2	1	3	30	25	56	60	45	42
INR increased\|	2	0	1	2	2	1	0	0	0	0	0	0	1	4	0	6
Proteinuria\|	2	0	0	0	4	3	0	0	1	0	1	0	2	2	2	4
Prothrombin time\|	2	0	1	3	3	1	0	0	1	1	0	1	4	4	2	5

Notes
[150] - Not all subjects had evaluable data for each parameter.
[151] - Not all subjects had evaluable data for each parameter.
[152] - Not all subjects had evaluable data for each parameter.
[153] - Not all subjects had evaluable data for each parameter.
[154] - Not all subjects had evaluable data for each parameter.
[155] - Not all subjects had evaluable data for each parameter.
[156] - Not all subjects had evaluable data for each parameter.
[157] - Not all subjects had evaluable data for each parameter.
[158] - Not all subjects had evaluable data for each parameter.
[159] - Not all subjects had evaluable data for each parameter.
[160] - Not all subjects had evaluable data for each parameter.
[161] - Not all subjects had evaluable data for each parameter.
[162] - Not all subjects had evaluable data for each parameter.
[163] - Not all subjects had evaluable data for each parameter.
[164] - Not all subjects had evaluable data for each parameter.
[165] - Not all subjects had evaluable data for each parameter.

No statistical analyses for this end point

Secondary: Number of Subjects with Vital Signs Data Meeting Pre-defined Criteria (Phase 1 and Phase 2)

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End point title

Number of Subjects with Vital Signs Data Meeting Pre-defined Criteria (Phase 1 and Phase 2) ^[166]

End point description

Blood pressure (BP), including systolic BP (SBP) and diastolic BP (DBP), and pulse rate were recorded in sitting position. Body weight was also measured. The safety analysis set included all enrolled subjects who received at least 1 dose of PF-06463922.

End point type

Secondary

End point timeframe

3 years

Notes
[166] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: All other reporting arms are not applicable to this end point.

End point values	10 mg QD (Phase 1)	25 mg QD (Phase 1)	50 mg QD (Phase 1)	75 mg QD (Phase 1)	100 mg QD (Phase 1)	150 mg QD (Phase 1)	200 mg QD (Phase 1)	35 mg BID (Phase 1)	75 mg BID (Phase 1)	100 mg BID (Phase 1)	EXP-1 (Phase 2)	EXP-2 (Phase 2)	EXP-3 (Phase 2)	EXP-4 (Phase 2)	EXP-5 (Phase 2)	EXP-6 (Phase 2)
Number of subjects analysed	3	3	3	12	17	3	3	3	3	4	30	26	60	65	45	46
Units: subjects
Sitting pulse rate <50 bpm\|	0	1	0	0	0	0	0	0	0	0	0	0	3	1	0	2
Sitting pulse rate >120 bpm\|	0	0	1	1	2	2	0	0	0	0	0	0	4	8	3	2
Increase in weight: 10% to <20%\|	1	1	0	6	6	2	2	0	1	0	9	12	14	18	15	12
Increase in weight: >=20%\|	0	1	1	1	4	1	0	0	0	1	8	1	4	9	3	8
Increase in sitting SBP >=40 mmHg\|	0	0	0	0	1	2	0	0	0	0	5	3	4	5	5	3
Increase in sitting SBP >=60 mmHg\|	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Increase in sitting DBP >=20 mmHg\|	0	2	0	0	7	3	1	0	0	0	9	9	16	12	10	11
Increase in sitting DBP >=40 mmHg\|	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	2
Increase in sitting pulse rate >=30 bpm\|	0	1	0	1	3	1	0	0	0	1	0	2	10	15	12	13
Decrease in weight >=10%\|	0	0	0	0	0	0	0	0	0	1	1	0	6	4	1	1
Decrease in SBP >=40 mmHg\|	0	0	0	3	2	1	0	0	0	0	0	1	2	1	1	3
Decrease in SBP >=60 mmHg\|	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Decrease in DBP >=20 mmHg\|	2	1	0	4	3	2	2	0	1	2	5	3	12	8	5	6
Decrease in DBP >=40 mmHg\|	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Decrease in sitting pulse rate >=30 bpm\|	0	0	1	2	0	1	0	1	1	1	7	2	4	5	3	5

No statistical analyses for this end point

Secondary: Number of Subjects with Maximum Decrease from Baseline Greater than or Equal to 20 Percent in Left Ventricular Ejection Fraction (LVEF) (Phase 1 and Phase 2)

Top of page

End point title

Number of Subjects with Maximum Decrease from Baseline Greater than or Equal to 20 Percent in Left Ventricular Ejection Fraction (LVEF) (Phase 1 and Phase 2) ^[167]

End point description

Left Ventricular Ejection Fraction (LVEF) was determined by electrocardiogram (ECG) measurement. Baseline was defined as the measurement prior to the first dose of study treatment. The safety analysis set included all enrolled subjects who received at least 1 dose of PF-06463922.

End point type

Secondary

End point timeframe

3 years

Notes
[167] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: All other reporting arms are not applicable to this end point.

End point values	10 mg QD (Phase 1)	25 mg QD (Phase 1)	50 mg QD (Phase 1)	75 mg QD (Phase 1)	100 mg QD (Phase 1)	150 mg QD (Phase 1)	200 mg QD (Phase 1)	35 mg BID (Phase 1)	75 mg BID (Phase 1)	100 mg BID (Phase 1)	EXP-1 (Phase 2)	EXP-2 (Phase 2)	EXP-3 (Phase 2)	EXP-4 (Phase 2)	EXP-5 (Phase 2)	EXP-6 (Phase 2)
Number of subjects analysed	3	3	3	12	17	3	3	3	3	4	30	27	60	65	46	47
Units: subjects	1	0	1	3	4	2	1	0	0	2	3	1	9	11	3	4

No statistical analyses for this end point

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Clinical trials

Clinical Trial Results: 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

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Number of Subjects with Cycle 1 Dose-Limiting Toxicities (DLTs) in Phase 1

Primary: Number of Subjects with Cycle 1 Dose-Limiting Toxicities (DLTs) in Phase 1

Primary: Percentage of Subjects with Overall and Intracranial Objective Response (Phase 2)

Primary: Percentage of Subjects with Overall and Intracranial Objective Response (Phase 2)

Secondary: Percentage of Subjects with Overall and Intracranial Objective Response (Phase 1)

Secondary: Percentage of Subjects with Overall and Intracranial Objective Response (Phase 1)

Secondary: Time to Tumor Response (TTR) and Intracranial TTR (Phase 1)

Secondary: Time to Tumor Response (TTR) and Intracranial TTR (Phase 1)

Secondary: Duration of Response (DOR) and Intracranial DOR (Phase 1)

Secondary: Duration of Response (DOR) and Intracranial DOR (Phase 1)

Secondary: Percentage of Subjects Achieving Disease Control and Intracranial Disease Control at 12 Weeks (Phase 1)

Secondary: Percentage of Subjects Achieving Disease Control and Intracranial Disease Control at 12 Weeks (Phase 1)

Secondary: Probability of First Event Being a Central Nervous System (CNS) Progression, Non CNS Progression, or Death (Phase 1)

Secondary: Probability of First Event Being a Central Nervous System (CNS) Progression, Non CNS Progression, or Death (Phase 1)

Secondary: Progression-Free Survival (PFS) (Phase 1)

Secondary: Progression-Free Survival (PFS) (Phase 1)

Secondary: Overall Survival (OS) (Phase 1)

Secondary: Overall Survival (OS) (Phase 1)

Secondary: Maximum Observed Plasma Concentration (Cmax) of PF-06463922 Following Single Oral Doses (Phase 1)

Secondary: Maximum Observed Plasma Concentration (Cmax) of PF-06463922 Following Single Oral Doses (Phase 1)

Secondary: Maximum Observed Plasma Concentration (Cmax) of PF-06463922 Following Multiple Oral Doses (Phase 1)

Secondary: Maximum Observed Plasma Concentration (Cmax) of PF-06463922 Following Multiple Oral Doses (Phase 1)

Secondary: Time for Cmax (Tmax) of PF-06463922 Following Single Oral Doses (Phase 1)

Secondary: Time for Cmax (Tmax) of PF-06463922 Following Single Oral Doses (Phase 1)

Secondary: Time for Cmax (Tmax) of PF-06463922 Following Multiple Oral Doses (Phase 1)

Secondary: Time for Cmax (Tmax) of PF-06463922 Following Multiple Oral Doses (Phase 1)

Secondary: Area under the Plasma Concentration-Time profile from Time Zero to Time Tau (AUCtau) of PF-06463922 Following Single Oral Doses (Phase 1)

Secondary: Area under the Plasma Concentration-Time profile from Time Zero to Time Tau (AUCtau) of PF-06463922 Following Single Oral Doses (Phase 1)

Secondary: Area under the Plasma Concentration-Time profile from Time Zero to Time Tau (AUCtau) of PF-06463922 Following Multiple Oral Doses (Phase 1)

Secondary: Area under the Plasma Concentration-Time profile from Time Zero to Time Tau (AUCtau) of PF-06463922 Following Multiple Oral Doses (Phase 1)

Secondary: Area under the Plasma Concentration-Time Profile from Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06463922 Following Single Oral Doses (Phase 1)

Secondary: Area under the Plasma Concentration-Time Profile from Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06463922 Following Single Oral Doses (Phase 1)

Secondary: Apparent Oral Clearance (CL/F) of PF-06463922 Following Single Oral Doses (Phase 1)

Secondary: Apparent Oral Clearance (CL/F) of PF-06463922 Following Single Oral Doses (Phase 1)

Secondary: Apparent Oral Clearance (CL/F) of PF-06463922 Following Multiple Oral Doses (Phase 1)

Secondary: Apparent Oral Clearance (CL/F) of PF-06463922 Following Multiple Oral Doses (Phase 1)

Secondary: Apparent Volume of Distribution (Vz/F) of PF-06463922 Following Single Oral Doses (Phase 1)

Secondary: Apparent Volume of Distribution (Vz/F) of PF-06463922 Following Single Oral Doses (Phase 1)

Secondary: Observed Accumulation Ratio (Rac) of PF-06463922 Following Multiple Oral Doses (Phase 1)

Secondary: Observed Accumulation Ratio (Rac) of PF-06463922 Following Multiple Oral Doses (Phase 1)

Secondary: Terminal Half-Life of PF-06463922 Following Single Oral Doses (Phase 1)

Secondary: Terminal Half-Life of PF-06463922 Following Single Oral Doses (Phase 1)

Secondary: Steady State Accumulation Ratio (Rss) of PF-06463922 Following Multiple Oral Doses (Phase 1)

Secondary: Steady State Accumulation Ratio (Rss) of PF-06463922 Following Multiple Oral Doses (Phase 1)

Secondary: Renal Clearance (CLr) of PF-06463922 (Phase 1)

Secondary: Renal Clearance (CLr) of PF-06463922 (Phase 1)

Secondary: Percent of PF-06463922 Recovered Unchanged in Urine up to Dosing Interval (AEtau%) (Phase 1)

Secondary: Percent of PF-06463922 Recovered Unchanged in Urine up to Dosing Interval (AEtau%) (Phase 1)

Secondary: Maximum Observed Plasma Concentration (Cmax) of Midazolam (Phase 1)

Secondary: Maximum Observed Plasma Concentration (Cmax) of Midazolam (Phase 1)

Secondary: Time for Cmax (Tmax) of Midazolam (Phase 1)

Secondary: Time for Cmax (Tmax) of Midazolam (Phase 1)

Secondary: Area under the Plasma Concentration-Time profile from Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Midazolam (Phase 1)

Secondary: Area under the Plasma Concentration-Time profile from Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Midazolam (Phase 1)

Secondary: Area under the Plasma Concentration-Time Profile from Time Zero Extrapolated to Infinite Time (AUCinf) of Midazolam (Phase 1)

Secondary: Area under the Plasma Concentration-Time Profile from Time Zero Extrapolated to Infinite Time (AUCinf) of Midazolam (Phase 1)

Secondary: Apparent Oral Clearance (CL/F) of Midazolam (Phase 1)

Secondary: Apparent Oral Clearance (CL/F) of Midazolam (Phase 1)

Secondary: Apparent Volume of Distribution (Vz/F) of Midazolam (Phase 1)

Secondary: Apparent Volume of Distribution (Vz/F) of Midazolam (Phase 1)

Secondary: Terminal Half-Life of Midazolam (Phase 1)

Secondary: Terminal Half-Life of Midazolam (Phase 1)

Secondary: Number of Subjects with ALK Mutation Based on Plasma CNA Analysis (Phase 1)

Secondary: Number of Subjects with ALK Mutation Based on Plasma CNA Analysis (Phase 1)

Secondary: Number of Subjects with ALK Mutation Based on Tumor Tissue Analysis (Phase 1)

Secondary: Number of Subjects with ALK Mutation Based on Tumor Tissue Analysis (Phase 1)

Secondary: Number of Subjects Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 1)

Secondary: Number of Subjects Who Improved, Worsened or Remained Stable in EORTC QLQ-C30 (Phase 1)

Secondary: Number of Subjects Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 1)

Secondary: Number of Subjects Who Improved, Worsened or Remained Stable in EORTC QLQ-LC13 (Phase 1)

Clinical Trial Results:
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