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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(current)
    This version publication date
    24 Mar 2018
    First version publication date
    24 Mar 2018
    Other versions

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    B7461001
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT01970865
    WHO universal trial number (UTN)
    -
    Sponsors
    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
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    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?
    No
    General information about the trial
    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
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    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
    89
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    270
    From 65 to 84 years
    61
    85 years and over
    1

    Subject disposition

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    Recruitment
    Recruitment details
    -

    Pre-assignment
    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
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    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.

    Arm title
    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.

    Arm title
    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.

    Arm title
    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.

    Arm title
    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.

    Arm title
    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.

    Arm title
    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.

    Arm title
    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.

    Arm title
    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.

    Arm title
    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.

    Arm title
    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.

    Arm title
    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.

    Arm title
    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.

    Arm title
    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.

    Arm title
    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.

    Arm title
    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.

    Arm title
    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
         Study ongoing
             -
             2
             -
             6
             8
             -
             2
             -
             1
             3
             29
             22
             43
             41
             29
             29
             2
         Adverse event, serious fatal
             3
             1
             3
             4
             6
             3
             1
             3
             2
             1
             1
             4
             14
             19
             15
             10
             1
         Unspecified
             -
             -
             -
             -
             -
             -
             -
             -
             -
             -
             -
             -
             -
             -
             -
             1
             -
         Consent withdrawn by subject
             -
             -
             -
             1
             2
             -
             -
             -
             -
             -
             -
             1
             2
             5
             2
             7
             -
         Lost to follow-up
             -
             -
             -
             1
             1
             -
             -
             -
             -
             -
             -
             -
             1
             -
             -
             -
             -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    10 mg QD (Phase 1)
    Reporting group 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.

    Reporting group title
    25 mg QD (Phase 1)
    Reporting group 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.

    Reporting group title
    50 mg QD (Phase 1)
    Reporting group 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.

    Reporting group title
    75 mg QD (Phase 1)
    Reporting group 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.

    Reporting group title
    100 mg QD (Phase 1)
    Reporting group 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.

    Reporting group title
    150 mg QD (Phase 1)
    Reporting group 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.

    Reporting group title
    200 mg QD (Phase 1)
    Reporting group 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.

    Reporting group title
    35 mg BID (Phase 1)
    Reporting group 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.

    Reporting group title
    75 mg BID (Phase 1)
    Reporting group 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.

    Reporting group title
    100 mg BID (Phase 1)
    Reporting group 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.

    Reporting group title
    EXP-1 (Phase 2)
    Reporting group 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.

    Reporting group title
    EXP-2 (Phase 2)
    Reporting group 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.

    Reporting group title
    EXP-3 (Phase 2)
    Reporting group 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.

    Reporting group title
    EXP-4 (Phase 2)
    Reporting group 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.

    Reporting group title
    EXP-5 (Phase 2)
    Reporting group 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.

    Reporting group title
    EXP-6 (Phase 2)
    Reporting group 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.

    Reporting group title
    Japan Lead-In Cohort (LIC)
    Reporting group 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.

    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 sets

    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

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    End points reporting groups
    Reporting group title
    10 mg QD (Phase 1)
    Reporting group 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.

    Reporting group title
    25 mg QD (Phase 1)
    Reporting group 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.

    Reporting group title
    50 mg QD (Phase 1)
    Reporting group 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.

    Reporting group title
    75 mg QD (Phase 1)
    Reporting group 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.

    Reporting group title
    100 mg QD (Phase 1)
    Reporting group 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.

    Reporting group title
    150 mg QD (Phase 1)
    Reporting group 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.

    Reporting group title
    200 mg QD (Phase 1)
    Reporting group 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.

    Reporting group title
    35 mg BID (Phase 1)
    Reporting group 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.

    Reporting group title
    75 mg BID (Phase 1)
    Reporting group 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.

    Reporting group title
    100 mg BID (Phase 1)
    Reporting group 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.

    Reporting group title
    EXP-1 (Phase 2)
    Reporting group 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.

    Reporting group title
    EXP-2 (Phase 2)
    Reporting group 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.

    Reporting group title
    EXP-3 (Phase 2)
    Reporting group 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.

    Reporting group title
    EXP-4 (Phase 2)
    Reporting group 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.

    Reporting group title
    EXP-5 (Phase 2)
    Reporting group 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.

    Reporting group title
    EXP-6 (Phase 2)
    Reporting group 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.

    Reporting group title
    Japan Lead-In Cohort (LIC)
    Reporting group 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.

    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.

    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
    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
    [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
    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
    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: nanogram*hour/milliliter (ng*hr/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
    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, 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
    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
    [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
    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
    [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
    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
    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
    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
    [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
    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
    [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
    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
    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
    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 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
    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
    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
    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
    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
    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 subjectswho 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: 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
    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
    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
    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.
    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
    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
    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
    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
    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
    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
    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)

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    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