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NCT01970865 · OUTCOME

Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study)

A Study Of PF-06463922 An ALK/ROS1 Inhibitor In Patients With Advanced Non Small Cell Lung Cancer With Specific Molecular Alterations · Source last updated 2024-08-12

Results reported by the registry submitting party. Population, time horizon, units and missing values must be read together.

Measure
COUNT_OF_PARTICIPANTS
Unit
Participants
Interval / dispersion
Not reported
Time frame
From first dose of study treatment to end of treatment (maximum of 8 years for Phase 1, maximum of 7.5 years for Phase 2 and up to a maximum of 6 years approx. for DDI sub study)

What was measured

Triplicate 12-lead electrocardiograms (ECGs) were performed approximately 2 minutes apart to determine mean QTc interval (QT interval corrected for heart rate). QT interval was corrected for heart rate using Fridericia's formula to provide QTcF. Absolute values and changes from baseline were summarized according to pre-defined criteria. Baseline was defined as the last evaluation on or prior to the first dose of study treatment.

Analysis population: The safety analysis set included all enrolled participants who received at least 1 dose of PF-06463922.

Groups in this outcome

10 mg QD (Phase 1)

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.

25 mg QD (Phase 1)

PF-06463922 25 mg was orally given 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.

50 mg QD (Phase 1)

PF-06463922 50 mg was orally given 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.

75 mg QD (Phase 1)

PF-06463922 75 mg was orally given 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.

100 mg QD (Phase 1)

PF-06463922 100 mg was orally given 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.

150 mg QD (Phase 1)

PF-06463922 150 mg was orally given 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.

200 mg QD (Phase 1)

PF-06463922 200 mg was orally given 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.

35 mg BID (Phase 1)

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.

75 mg BID (Phase 1)

PF-06463922 75 mg was orally given 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.

100 mg BID (Phase 1)

PF-06463922 100 mg was orally given 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.

EXP-1 (Phase 2)

Treatment-naïve participants with advanced anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC) with or without asymptomatic central nervous system (CNS) metastases were given PF-06463922 100 mg orally QD on Day -7 (only participants 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.

EXP-2 (Phase 2)

Participants with advanced ALK-positive NSCLC with or without asymptomatic CNS metastases relapsing after only crizotinib therapy were given PF-06463922 100 mg orally QD on Day -7 (only for participants 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.

EXP-3 (Phase 2)

Participants 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 participants 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 QD on Day -7 (only for participants 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.

EXP-4 (Phase 2)

Participants 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 QD on Day -7 (only for participants 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.

EXP-5 (Phase 2)

Participants 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 QD on Day -7 (only for participant 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.

EXP-6 (Phase 2)

Participants 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 QD on Day -7 (only for participants 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.

DDI Sub-study

Participants with advanced ALK positive or ROS1-positive NSCLC who were treatment naïve or had any number of prior cancer therapies with or without asymptomatic CNS metastases were administered a single dose of a probe substrate alone on Day -2. Participants were given PF-06463922 100 mg orally QD starting on Cycle1 Day 1 and along with probe substrate on Day 15 Cycle 1.

Group identifiers and denominators belong to this outcome only. They may differ in another outcome or in safety reporting.

Analysis denominator · Participants

GroupSource count
10 mg QD (Phase 1)3
25 mg QD (Phase 1)3
50 mg QD (Phase 1)3
75 mg QD (Phase 1)12
100 mg QD (Phase 1)17
150 mg QD (Phase 1)3
200 mg QD (Phase 1)3
35 mg BID (Phase 1)3
75 mg BID (Phase 1)3
100 mg BID (Phase 1)4
EXP-1 (Phase 2)30
EXP-2 (Phase 2)27
EXP-3 (Phase 2)60
EXP-4 (Phase 2)65
EXP-5 (Phase 2)46
EXP-6 (Phase 2)47
DDI Sub-study32

Reported measurements

QTcF: 450 to <480 msec
Values in Participants · Interval/dispersion: Not reported
GroupValueSpreadLowerUpperComment
10 mg QD (Phase 1)1Not reportedNot reportedNot reportedNot reported
25 mg QD (Phase 1)0Not reportedNot reportedNot reportedNot reported
50 mg QD (Phase 1)0Not reportedNot reportedNot reportedNot reported
75 mg QD (Phase 1)2Not reportedNot reportedNot reportedNot reported
100 mg QD (Phase 1)1Not reportedNot reportedNot reportedNot reported
150 mg QD (Phase 1)1Not reportedNot reportedNot reportedNot reported
200 mg QD (Phase 1)0Not reportedNot reportedNot reportedNot reported
35 mg BID (Phase 1)2Not reportedNot reportedNot reportedNot reported
75 mg BID (Phase 1)0Not reportedNot reportedNot reportedNot reported
100 mg BID (Phase 1)1Not reportedNot reportedNot reportedNot reported
EXP-1 (Phase 2)5Not reportedNot reportedNot reportedNot reported
EXP-2 (Phase 2)8Not reportedNot reportedNot reportedNot reported
EXP-3 (Phase 2)11Not reportedNot reportedNot reportedNot reported
EXP-4 (Phase 2)9Not reportedNot reportedNot reportedNot reported
EXP-5 (Phase 2)13Not reportedNot reportedNot reportedNot reported
EXP-6 (Phase 2)9Not reportedNot reportedNot reportedNot reported
DDI Sub-study7Not reportedNot reportedNot reportedNot reported
QTcF: 480 to <500 msec
Values in Participants · Interval/dispersion: Not reported
GroupValueSpreadLowerUpperComment
10 mg QD (Phase 1)1Not reportedNot reportedNot reportedNot reported
25 mg QD (Phase 1)0Not reportedNot reportedNot reportedNot reported
50 mg QD (Phase 1)0Not reportedNot reportedNot reportedNot reported
75 mg QD (Phase 1)0Not reportedNot reportedNot reportedNot reported
100 mg QD (Phase 1)0Not reportedNot reportedNot reportedNot reported
150 mg QD (Phase 1)0Not reportedNot reportedNot reportedNot reported
200 mg QD (Phase 1)0Not reportedNot reportedNot reportedNot reported
35 mg BID (Phase 1)0Not reportedNot reportedNot reportedNot reported
75 mg BID (Phase 1)0Not reportedNot reportedNot reportedNot reported
100 mg BID (Phase 1)1Not reportedNot reportedNot reportedNot reported
EXP-1 (Phase 2)1Not reportedNot reportedNot reportedNot reported
EXP-2 (Phase 2)1Not reportedNot reportedNot reportedNot reported
EXP-3 (Phase 2)3Not reportedNot reportedNot reportedNot reported
EXP-4 (Phase 2)0Not reportedNot reportedNot reportedNot reported
EXP-5 (Phase 2)1Not reportedNot reportedNot reportedNot reported
EXP-6 (Phase 2)1Not reportedNot reportedNot reportedNot reported
DDI Sub-study1Not reportedNot reportedNot reportedNot reported
QTcF: >=500 msec
Values in Participants · Interval/dispersion: Not reported
GroupValueSpreadLowerUpperComment
10 mg QD (Phase 1)0Not reportedNot reportedNot reportedNot reported
25 mg QD (Phase 1)0Not reportedNot reportedNot reportedNot reported
50 mg QD (Phase 1)0Not reportedNot reportedNot reportedNot reported
75 mg QD (Phase 1)0Not reportedNot reportedNot reportedNot reported
100 mg QD (Phase 1)0Not reportedNot reportedNot reportedNot reported
150 mg QD (Phase 1)0Not reportedNot reportedNot reportedNot reported
200 mg QD (Phase 1)0Not reportedNot reportedNot reportedNot reported
35 mg BID (Phase 1)0Not reportedNot reportedNot reportedNot reported
75 mg BID (Phase 1)0Not reportedNot reportedNot reportedNot reported
100 mg BID (Phase 1)0Not reportedNot reportedNot reportedNot reported
EXP-1 (Phase 2)0Not reportedNot reportedNot reportedNot reported
EXP-2 (Phase 2)0Not reportedNot reportedNot reportedNot reported
EXP-3 (Phase 2)1Not reportedNot reportedNot reportedNot reported
EXP-4 (Phase 2)1Not reportedNot reportedNot reportedNot reported
EXP-5 (Phase 2)1Not reportedNot reportedNot reportedNot reported
EXP-6 (Phase 2)0Not reportedNot reportedNot reportedNot reported
DDI Sub-study1Not reportedNot reportedNot reportedNot reported
QTcF Increase: 30 to <60 msec
Values in Participants · Interval/dispersion: Not reported
GroupValueSpreadLowerUpperComment
10 mg QD (Phase 1)0Not reportedNot reportedNot reportedNot reported
25 mg QD (Phase 1)0Not reportedNot reportedNot reportedNot reported
50 mg QD (Phase 1)1Not reportedNot reportedNot reportedNot reported
75 mg QD (Phase 1)3Not reportedNot reportedNot reportedNot reported
100 mg QD (Phase 1)3Not reportedNot reportedNot reportedNot reported
150 mg QD (Phase 1)0Not reportedNot reportedNot reportedNot reported
200 mg QD (Phase 1)0Not reportedNot reportedNot reportedNot reported
35 mg BID (Phase 1)1Not reportedNot reportedNot reportedNot reported
75 mg BID (Phase 1)0Not reportedNot reportedNot reportedNot reported
100 mg BID (Phase 1)1Not reportedNot reportedNot reportedNot reported
EXP-1 (Phase 2)10Not reportedNot reportedNot reportedNot reported
EXP-2 (Phase 2)8Not reportedNot reportedNot reportedNot reported
EXP-3 (Phase 2)18Not reportedNot reportedNot reportedNot reported
EXP-4 (Phase 2)20Not reportedNot reportedNot reportedNot reported
EXP-5 (Phase 2)7Not reportedNot reportedNot reportedNot reported
EXP-6 (Phase 2)12Not reportedNot reportedNot reportedNot reported
DDI Sub-study7Not reportedNot reportedNot reportedNot reported
QTcF: >=60 msec
Values in Participants · Interval/dispersion: Not reported
GroupValueSpreadLowerUpperComment
10 mg QD (Phase 1)0Not reportedNot reportedNot reportedNot reported
25 mg QD (Phase 1)0Not reportedNot reportedNot reportedNot reported
50 mg QD (Phase 1)0Not reportedNot reportedNot reportedNot reported
75 mg QD (Phase 1)0Not reportedNot reportedNot reportedNot reported
100 mg QD (Phase 1)0Not reportedNot reportedNot reportedNot reported
150 mg QD (Phase 1)0Not reportedNot reportedNot reportedNot reported
200 mg QD (Phase 1)0Not reportedNot reportedNot reportedNot reported
35 mg BID (Phase 1)0Not reportedNot reportedNot reportedNot reported
75 mg BID (Phase 1)0Not reportedNot reportedNot reportedNot reported
100 mg BID (Phase 1)1Not reportedNot reportedNot reportedNot reported
EXP-1 (Phase 2)0Not reportedNot reportedNot reportedNot reported
EXP-2 (Phase 2)0Not reportedNot reportedNot reportedNot reported
EXP-3 (Phase 2)1Not reportedNot reportedNot reportedNot reported
EXP-4 (Phase 2)1Not reportedNot reportedNot reportedNot reported
EXP-5 (Phase 2)3Not reportedNot reportedNot reportedNot reported
EXP-6 (Phase 2)1Not reportedNot reportedNot reportedNot reported
DDI Sub-study1Not reportedNot reportedNot reportedNot reported
Complete source fields
classes
  1. categories
    1. measurements
      1. group Id
        OG000
        value
        1
      2. group Id
        OG001
        value
        0
      3. group Id
        OG002
        value
        0
      4. group Id
        OG003
        value
        2
      5. group Id
        OG004
        value
        1
      6. group Id
        OG005
        value
        1
      7. group Id
        OG006
        value
        0
      8. group Id
        OG007
        value
        2
      9. group Id
        OG008
        value
        0
      10. group Id
        OG009
        value
        1
      11. group Id
        OG010
        value
        5
      12. group Id
        OG011
        value
        8
    title
    QTcF: 450 to <480 msec
  2. categories
    1. measurements
      1. group Id
        OG000
        value
        1
      2. group Id
        OG001
        value
        0
      3. group Id
        OG002
        value
        0
      4. group Id
        OG003
        value
        0
      5. group Id
        OG004
        value
        0
      6. group Id
        OG005
        value
        0
      7. group Id
        OG006
        value
        0
      8. group Id
        OG007
        value
        0
      9. group Id
        OG008
        value
        0
      10. group Id
        OG009
        value
        1
      11. group Id
        OG010
        value
        1
      12. group Id
        OG011
        value
        1
    title
    QTcF: 480 to <500 msec
  3. categories
    1. measurements
      1. group Id
        OG000
        value
        0
      2. group Id
        OG001
        value
        0
      3. group Id
        OG002
        value
        0
      4. group Id
        OG003
        value
        0
      5. group Id
        OG004
        value
        0
      6. group Id
        OG005
        value
        0
      7. group Id
        OG006
        value
        0
      8. group Id
        OG007
        value
        0
      9. group Id
        OG008
        value
        0
      10. group Id
        OG009
        value
        0
      11. group Id
        OG010
        value
        0
      12. group Id
        OG011
        value
        0
    title
    QTcF: >=500 msec
  4. categories
    1. measurements
      1. group Id
        OG000
        value
        0
      2. group Id
        OG001
        value
        0
      3. group Id
        OG002
        value
        1
      4. group Id
        OG003
        value
        3
      5. group Id
        OG004
        value
        3
      6. group Id
        OG005
        value
        0
      7. group Id
        OG006
        value
        0
      8. group Id
        OG007
        value
        1
      9. group Id
        OG008
        value
        0
      10. group Id
        OG009
        value
        1
      11. group Id
        OG010
        value
        10
      12. group Id
        OG011
        value
        8
    title
    QTcF Increase: 30 to <60 msec
  5. categories
    1. measurements
      1. group Id
        OG000
        value
        0
      2. group Id
        OG001
        value
        0
      3. group Id
        OG002
        value
        0
      4. group Id
        OG003
        value
        0
      5. group Id
        OG004
        value
        0
      6. group Id
        OG005
        value
        0
      7. group Id
        OG006
        value
        0
      8. group Id
        OG007
        value
        0
      9. group Id
        OG008
        value
        0
      10. group Id
        OG009
        value
        1
      11. group Id
        OG010
        value
        0
      12. group Id
        OG011
        value
        0
    title
    QTcF: >=60 msec
denoms
  1. counts
    1. group Id
      OG000
      value
      3
    2. group Id
      OG001
      value
      3
    3. group Id
      OG002
      value
      3
    4. group Id
      OG003
      value
      12
    5. group Id
      OG004
      value
      17
    6. group Id
      OG005
      value
      3
    7. group Id
      OG006
      value
      3
    8. group Id
      OG007
      value
      3
    9. group Id
      OG008
      value
      3
    10. group Id
      OG009
      value
      4
    11. group Id
      OG010
      value
      30
    12. group Id
      OG011
      value
      27
    units
    Participants
description
Triplicate 12-lead electrocardiograms (ECGs) were performed approximately 2 minutes apart to determine mean QTc interval (QT interval corrected for heart rate). QT interval was corrected for heart rate using Fridericia's formula to provide QTcF. Absolute values and changes from baseline were summarized according to pre-defined criteria. Baseline was defined as the last evaluation on or prior to the first dose of study treatment.
groups
  1. 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.
    id
    OG000
    title
    10 mg QD (Phase 1)
  2. description
    PF-06463922 25 mg was orally given 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.
    id
    OG001
    title
    25 mg QD (Phase 1)
  3. description
    PF-06463922 50 mg was orally given 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.
    id
    OG002
    title
    50 mg QD (Phase 1)
  4. description
    PF-06463922 75 mg was orally given 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.
    id
    OG003
    title
    75 mg QD (Phase 1)
  5. description
    PF-06463922 100 mg was orally given 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.
    id
    OG004
    title
    100 mg QD (Phase 1)
  6. description
    PF-06463922 150 mg was orally given 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.
    id
    OG005
    title
    150 mg QD (Phase 1)
  7. description
    PF-06463922 200 mg was orally given 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.
    id
    OG006
    title
    200 mg QD (Phase 1)
  8. 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.
    id
    OG007
    title
    35 mg BID (Phase 1)
  9. description
    PF-06463922 75 mg was orally given 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.
    id
    OG008
    title
    75 mg BID (Phase 1)
  10. description
    PF-06463922 100 mg was orally given 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.
    id
    OG009
    title
    100 mg BID (Phase 1)
  11. description
    Treatment-naïve participants with advanced anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC) with or without asymptomatic central nervous system (CNS) metastases were given PF-06463922 100 mg orally QD on Day -7 (only participants 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.
    id
    OG010
    title
    EXP-1 (Phase 2)
  12. description
    Participants with advanced ALK-positive NSCLC with or without asymptomatic CNS metastases relapsing after only crizotinib therapy were given PF-06463922 100 mg orally QD on Day -7 (only for participants 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.
    id
    OG011
    title
    EXP-2 (Phase 2)
param Type
COUNT_OF_PARTICIPANTS
population Description
The safety analysis set included all enrolled participants who received at least 1 dose of PF-06463922.
reporting Status
POSTED
time Frame
From first dose of study treatment to end of treatment (maximum of 8 years for Phase 1, maximum of 7.5 years for Phase 2 and up to a maximum of 6 years approx. for DDI sub study)
title
Number of Participants With Absolute Values and Change From Baseline in QTcF Meeting Pre-defined Criteria (Phase 1, Phase 2 and DDI Sub-study)
type
SECONDARY
unit Of Measure
Participants

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Preserved source evidence · Not medical advice