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A Study to Evaluate the Efficacy of Brigatinib (AP26113) in Participants With Anaplastic Lymphoma Kinase (ALK)-Positive, Non-small Cell Lung Cancer (NSCLC) Previously Treated With Crizotinib

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ClinicalTrials.gov Identifier: NCT02094573
Recruitment Status : Completed
First Posted : March 24, 2014
Results First Posted : June 21, 2017
Last Update Posted : March 15, 2021
Sponsor:
Information provided by (Responsible Party):
Takeda ( Ariad Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Carcinoma, Non-Small-Cell Lung
Intervention Drug: Brigatinib
Enrollment 222
Recruitment Details Participants took part in the study at 71 investigative sites in the United States, Canada, Europe, Australia, and Asia from 04 Jun 2014 to 27 February 2020.
Pre-assignment Details Participants with diagnosis of anaplastic lymphoma kinase (ALK)-positive, non-small cell lung cancer (NSCLC) who had progressed on crizotinib were enrolled to receive brigatinib 90 mg, once daily or brigatinib 90-180 mg, once daily.
Arm/Group Title Brigatinib 90 mg Brigatinib 90 mg - 180 mg
Hide Arm/Group Description Brigatinib 90 mg, tablets, orally, once daily in each Cycle of 28 days until disease progression or intolerable toxicity (median duration of exposure was 402 days). Brigatinib 90 mg, tablets, orally, once daily for 7 days followed by brigatinib 180 mg, orally once daily in Cycle 1 of 28 days followed by brigatinib 180 mg, orally once daily in Cycle 2 and onward Cycles of 28 days until disease progression or intolerable toxicity (median duration of exposure was 522 days).
Period Title: Overall Study
Started 112 110
Treated 109 110
Completed [1] 0 0
Not Completed 112 110
Reason Not Completed
Adverse Event             4             14
Clinical Progressive Disease             9             13
Death             11             3
Documented Progressive Disease (RECIST 1.1)             63             50
Non-compliance with Study Drug             1             1
Subject Received a New Systemic Anticancer Therapy             1             0
Physician Decision             4             4
Site Terminated by Sponsor             10             17
Withdrawal by Subject             6             8
Randomized but not Treated             3             0
[1]
Completed = Participants who completed the treatment.
Arm/Group Title Brigatinib 90 mg Brigatinib 90 mg - 180 mg Total
Hide Arm/Group Description Brigatinib 90 mg, tablets, orally, once daily in each Cycle of 28 days until disease progression or intolerable toxicity (median duration of exposure was 402 days). Brigatinib 90 mg, tablets, orally, once daily for 7 days followed by brigatinib 180 mg, orally once daily in Cycle 1 of 28 days followed by brigatinib 180 mg, orally once daily in Cycle 2 and onward Cycles of 28 days until disease progression or intolerable toxicity (median duration of exposure was 522 days). Total of all reporting groups
Overall Number of Baseline Participants 112 110 222
Hide Baseline Analysis Population Description
Intention to Treat (ITT) Population included all participants who were randomized to each regimen regardless of whether they received study drug or adhere to the assigned dose.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 112 participants 110 participants 222 participants
51.5  (13.03) 55.4  (12.98) 53.4  (13.13)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 112 participants 110 participants 222 participants
Female
62
  55.4%
64
  58.2%
126
  56.8%
Male
50
  44.6%
46
  41.8%
96
  43.2%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 112 participants 110 participants 222 participants
White
72
  64.3%
76
  69.1%
148
  66.7%
Black or African American
1
   0.9%
2
   1.8%
3
   1.4%
Asian
39
  34.8%
30
  27.3%
69
  31.1%
Unknown
0
   0.0%
2
   1.8%
2
   0.9%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 112 participants 110 participants 222 participants
Hispanic or Latino
5
   4.5%
8
   7.3%
13
   5.9%
Not Hispanic or Latino
107
  95.5%
102
  92.7%
209
  94.1%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 112 participants 110 participants 222 participants
Australia
3
   2.7%
6
   5.5%
9
   4.1%
Austria
3
   2.7%
6
   5.5%
9
   4.1%
Belgium
3
   2.7%
2
   1.8%
5
   2.3%
Canada
2
   1.8%
1
   0.9%
3
   1.4%
Denmark
2
   1.8%
6
   5.5%
8
   3.6%
France
4
   3.6%
2
   1.8%
6
   2.7%
Germany
7
   6.3%
7
   6.4%
14
   6.3%
Hong Kong
6
   5.4%
0
   0.0%
6
   2.7%
Italy
15
  13.4%
14
  12.7%
29
  13.1%
Netherlands
6
   5.4%
6
   5.5%
12
   5.4%
Norway
1
   0.9%
1
   0.9%
2
   0.9%
Singapore
4
   3.6%
3
   2.7%
7
   3.2%
Spain
5
   4.5%
7
   6.4%
12
   5.4%
Sweden
2
   1.8%
2
   1.8%
4
   1.8%
Switzerland
0
   0.0%
1
   0.9%
1
   0.5%
United Kingdom
2
   1.8%
1
   0.9%
3
   1.4%
United States
21
  18.8%
25
  22.7%
46
  20.7%
Korea, Republic Of
26
  23.2%
20
  18.2%
46
  20.7%
1.Primary Outcome
Title Confirmed Objective Response Rate (ORR) as Assessed by Investigator
Hide Description ORR assessed by the investigator, was defined as percentage of the participants with confirmed complete response (CR) or partial response (PR) according to response evaluation criteria in solid tumors (RECIST) v1.1 (confirmed ≥4 weeks after initial response), after initiation of study treatment. CR for target lesion: disappearance of all extranodal lesions and all pathological lymph nodes must have decreased to <10 mm in short axis. CR for non-target lesion: Disappearance of all extranodal non-target lesions, all lymph nodes must be non-pathological in size (<10mm short axis) and norrmalization of tumor marker level. PR: at least 30% decrease in the sum of the longest diameters (SLD) of target lesions, taking as reference the baseline sum diameters. The exact 2-sided 97.5% confidence interval was calculated. The treatment regimen was considered to have achieved the primary objective when lower bound of the 97.5% confidence interval for ORR assessed by investigator is greater than 20%.
Time Frame Screening, at 8-week intervals thereafter (on Day 1 of every odd-numbered Cycle of 28-days) through 15 Cycles and every 3 Cycles thereafter until disease progression or up to end of the study (approximately up to 69 months)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population included all participants who were randomized to each regimen regardless of whether they received study drug or adhered to the assigned dose.
Arm/Group Title Brigatinib 90 mg Brigatinib 90 mg - 180 mg
Hide Arm/Group Description:
Brigatinib 90 mg, tablets, orally, once daily in each Cycle of 28 days until disease progression or intolerable toxicity (median duration of exposure was 402 days).
Brigatinib 90 mg, tablets, orally, once daily for 7 days followed by brigatinib 180 mg, orally once daily in Cycle 1 of 28 days followed by brigatinib 180 mg, orally once daily in Cycle 2 and onward Cycles of 28 days until disease progression or intolerable toxicity (median duration of exposure was 522 days).
Overall Number of Participants Analyzed 112 110
Measure Type: Number
Number (97.5% Confidence Interval)
Unit of Measure: percentage of participants
45.5
(34.8 to 56.5)
57.3
(46.1 to 67.9)
2.Secondary Outcome
Title Confirmed Objective Response Rate (ORR) as Assessed by Independent Review Committee (IRC)
Hide Description ORR assessed by the IRC, was defined as the percentage of the participants with CR or PR according to RECIST v1.1 (confirmed ≥4 weeks after initial response), after the initiation of study treatment. CR for target lesion: disappearance of all extranodal lesions and all pathological lymph nodes must have decreased to <10 mm in short axis. CR for non-target lesion: Disappearance of all extranodal non-target lesions, all lymph nodes must be non-pathological in size (<10mm short axis) and norrmalization of tumor marker level. PR: at least a 30% decrease in theSLD of target lesions, taking as reference the baseline sum diameters. The exact 2-sided 95% confidence interval was calculated.
Time Frame Screening, at 8-week intervals thereafter (on Day 1 of every odd-numbered Cycle of 28-days) through 15 Cycles and every 3 Cycles thereafter until disease progression or up to end of the study (approximately up to 69 months)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population included all participants who were randomized to each regimen regardless of whether they received study drug or adhered to the assigned dose.
Arm/Group Title Brigatinib 90 mg Brigatinib 90 mg - 180 mg
Hide Arm/Group Description:
Brigatinib 90 mg, tablets, orally, once daily in each Cycle of 28 days until disease progression or intolerable toxicity (median duration of exposure was 402 days).
Brigatinib 90 mg, tablets, orally, once daily for 7 days followed by brigatinib 180 mg, orally once daily in Cycle 1 of 28 days followed by brigatinib 180 mg, orally once daily in Cycle 2 and onward Cycles of 28 days until disease progression or intolerable toxicity (median duration of exposure was 522 days).
Overall Number of Participants Analyzed 112 110
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
51.8
(42.1 to 61.3)
56.4
(46.6 to 65.8)
3.Secondary Outcome
Title Confirmed Intracranial Central Nervous System Objective Response Rate (CNS ORR) in Participants With Measurable Active Brain Metastases
Hide Description Confirmed intracranial CNS ORR was defined as the percentage of the participants with CR or PR in the intracranial CNS per modification of RECIST v1.1 as evaluated by IRC after the initiation of study drug. Confirmed responses were those that persisted on repeat imaging 4 weeks or more after initial response. CR for target lesion: disappearance of all extranodal non-target lesions, all lymph nodes must be non-pathological in size (<10mm short axis). CR for non-target lesion: disappearance of all extranodal non-target lesions, all lymph nodes must be non-pathological in size (<10mm short axis) and norrmalization of tumor marker level. PR: at least a 30% decrease in the SLD of target lesions, taking as reference the Baseline sum diameters.
Time Frame Screening, at 8-week intervals thereafter (on Day 1 of every odd-numbered Cycle of 28-days) through 15 Cycles and every 3 Cycles thereafter until disease progression or approximately up to 29 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population included all participants who were randomized to each regimen regardless of whether they received study drug or adhered to the assigned dose. Participants with measurable active brain metastases at Baseline were evaluated for this outcome measure.
Arm/Group Title Brigatinib 90 mg Brigatinib 90 mg - 180 mg
Hide Arm/Group Description:
Brigatinib 90 mg, tablets, orally, once daily in each Cycle of 28 days until disease progression or intolerable toxicity (median duration of exposure was 402 days).
Brigatinib 90 mg, tablets, orally, once daily for 7 days followed by brigatinib 180 mg, orally once daily in Cycle 1 of 28 days followed by brigatinib 180 mg, orally once daily in Cycle 2 and onward Cycles of 28 days until disease progression or intolerable toxicity (median duration of exposure was 522 days).
Overall Number of Participants Analyzed 19 15
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
47.4
(24.4 to 71.1)
73.3
(44.9 to 92.2)
4.Secondary Outcome
Title Confirmed Intracranial Central Nervous System Objective Response Rate (CNS ORR) in Participants With Only Non-measurable Active Brain Metastases
Hide Description Confirmed intracranial CNS ORR is defined as the percentage of the participants with CR or PR in the intracranial CNS per modification of RECIST v1.1 as evaluated by IRC after the initiation of study drug. Confirmed responses were those that persisted on repeat imaging 4 weeks or more after initial response. CR for target lesion: disappearance of all extranodal non-target lesions, all lymph nodes must be non-pathological in size (<10mm short axis). CR for non-target lesion: disappearance of all extranodal non-target lesions, all lymph nodes must be non-pathological in size (<10mm short axis) and norrmalization of tumor marker level. PR: at least a 30% decrease in the SLD of target lesions, taking as reference the Baseline sum diameters.
Time Frame Screening, at 8-week intervals thereafter (on Day 1 of every odd-numbered Cycle of 28-days) through 15 Cycles and every 3 Cycles thereafter until disease progression or approximately up to 29 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population included all participants who were randomized to each regimen regardless of whether they received study drug or adhered to the assigned dose. Participants with only non-measurable active brain metastases at Baseline were evaluated for this outcome measure.
Arm/Group Title Brigatinib 90 mg Brigatinib 90 mg - 180 mg
Hide Arm/Group Description:
Brigatinib 90 mg, tablets, orally, once daily in each Cycle of 28 days until disease progression or intolerable toxicity (median duration of exposure was 402 days).
Brigatinib 90 mg, tablets, orally, once daily for 7 days followed by brigatinib 180 mg, orally once daily in Cycle 1 of 28 days followed by brigatinib 180 mg, orally once daily in Cycle 2 and onward Cycles of 28 days until disease progression or intolerable toxicity (median duration of exposure was 522 days).
Overall Number of Participants Analyzed 33 36
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
12.1
(3.4 to 28.2)
16.7
(6.4 to 32.8)
5.Secondary Outcome
Title Intracranial CNS Progression Free Survival (PFS) in Participants With Active Brain Metastases
Hide Description Intracranial CNS PFS as evaluated by IRC is defined as the time interval from the date of the first dose of the study drug until the first date at which intracranial CNS disease progression, an increase of 20% or more in the sum of diameters of intracranial CNS target lesions, unequivocal progression of non-target lesions, or the appearance of new lesions in the intracranial CNS, was objectively documented by a scan, or death due to any cause, whichever occurred first. The analysis was based on the Kaplan-Meier (KM) Estimates.
Time Frame Screening, at 8-week intervals thereafter (on Day 1 of every odd-numbered Cycle of 28-days) through 15 Cycles and every 3 Cycles thereafter until disease progression or approximately up to 29 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population included all participants who were randomized to each regimen regardless of whether they received study drug or adhered to the assigned dose. Participants with active brain metastases whether it was measurable or non-measurable at baseline were evaluated for this outcome measure.
Arm/Group Title Brigatinib 90 mg Brigatinib 90 mg - 180 mg
Hide Arm/Group Description:
Brigatinib 90 mg, tablets, orally, once daily in each Cycle of 28 days until disease progression or intolerable toxicity (median duration of exposure was 402 days).
Brigatinib 90 mg, tablets, orally, once daily for 7 days followed by brigatinib 180 mg, orally once daily in Cycle 1 of 28 days followed by brigatinib 180 mg, orally once daily in Cycle 2 and onward Cycles of 28 days until disease progression or intolerable toxicity (median duration of exposure was 522 days).
Overall Number of Participants Analyzed 52 51
Median (95% Confidence Interval)
Unit of Measure: months
12.8
(9.0 to 18.4)
12.8
(9.1 to 21.1)
6.Secondary Outcome
Title Time to Response
Hide Description Time to response was defined as the time interval from the date of the first dose of the study drug until the initial observation of CR or PR for participants with confirmed CR/PR. CR for target lesion: disappearance of all extranodal lesions and all pathological lymph nodes must have decreased to <10 mm in short axis. CR for non-target lesion: Disappearance of all extranodal non-target lesions, all lymph nodes must be non-pathological in size (<10mm short axis) and norrmalization of tumor marker level. PR: at least a 30% decrease in the SLD of target lesions, taking as reference the Baseline sum diameters.
Time Frame Up to approximately 69 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population included all participants who were randomized to each regimen regardless of whether they received study drug or adhered to the assigned dose. Participants who had confirmed CR or PR were evaluable for this outcome measure.
Arm/Group Title Brigatinib 90 mg Brigatinib 90 mg - 180 mg
Hide Arm/Group Description:
Brigatinib 90 mg, tablets, orally, once daily in each Cycle of 28 days until disease progression or intolerable toxicity (median duration of exposure was 402 days).
Brigatinib 90 mg, tablets, orally, once daily for 7 days followed by brigatinib 180 mg, orally once daily in Cycle 1 of 28 days followed by brigatinib 180 mg, orally once daily in Cycle 2 and onward Cycles of 28 days until disease progression or intolerable toxicity (median duration of exposure was 522 days).
Overall Number of Participants Analyzed 51 63
Median (Full Range)
Unit of Measure: months
1.8
(1.7 to 11.1)
1.9
(1.0 to 35.0)
7.Secondary Outcome
Title Duration of Response
Hide Description Duration of response was defined as the time interval from the time that the measurement criteria are first met for CR/PR (whichever is first recorded) until the first date that the progressive disease is objectively documented or death. Patients without progressive disease or death were censored at the last valid response assessment. CR for target lesion: disappearance of all extranodal lesions and all pathological lymph nodes must have decreased to <10 mm in short axis. CR for non-target lesion: Disappearance of all extranodal non-target lesions, all lymph nodes must be non-pathological in size (<10mm short axis) and norrmalization of tumor marker level. PR: at least a 30% decrease in the SLD of target lesions, taking as reference the baseline sum diameters. The analysis was based on the Kaplan-Meier (KM) Estimates.
Time Frame Up to approximately 69 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population included all participants who were randomized to each regimen regardless of whether they received study drug or adhered to the assigned dose. Participants who had confirmed CR or PR were evaluable for this outcome measure.
Arm/Group Title Brigatinib 90 mg Brigatinib 90 mg - 180 mg
Hide Arm/Group Description:
Brigatinib 90 mg, tablets, orally, once daily in each Cycle of 28 days until disease progression or intolerable toxicity (median duration of exposure was 402 days).
Brigatinib 90 mg, tablets, orally, once daily for 7 days followed by brigatinib 180 mg, orally once daily in Cycle 1 of 28 days followed by brigatinib 180 mg, orally once daily in Cycle 2 and onward Cycles of 28 days until disease progression or intolerable toxicity (median duration of exposure was 522 days).
Overall Number of Participants Analyzed 51 63
Median (95% Confidence Interval)
Unit of Measure: months
12.0
(9.2 to 19.4)
13.8
(10.8 to 17.6)
8.Secondary Outcome
Title Time on Treatment
Hide Description Time on treatment was defined as the time from the first to the last dose of study drug. For participants who have not discontinued, time on treatment was censored as of the last dose of the study drug.
Time Frame Up to approximately 69 months
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population included all participants who received at least one dose of study drug.
Arm/Group Title Brigatinib 90 mg Brigatinib 90 mg - 180 mg
Hide Arm/Group Description:
Brigatinib 90 mg, tablets, orally, once daily in each Cycle of 28 days until disease progression or intolerable toxicity (median duration of exposure was 402 days).
Brigatinib 90 mg, tablets, orally, once daily for 7 days followed by brigatinib 180 mg, orally once daily in Cycle 1 of 28 days followed by brigatinib 180 mg, orally once daily in Cycle 2 and onward Cycles of 28 days until disease progression or intolerable toxicity (median duration of exposure was 522 days).
Overall Number of Participants Analyzed 109 110
Median (Full Range)
Unit of Measure: days
402.0
(1 to 1882)
522.0
(2 to 2030)
9.Secondary Outcome
Title Disease Control Rate (DCR)
Hide Description DCR was defined as the percentage of randomized participants who were confirmed to have achieved CR or PR or have a best overall response as stable disease (SD) for 6 weeks or more after initiation of the study drug. CR for target lesion: disappearance of all extranodal lesions and all pathological lymph nodes must have decreased to <10 mm in short axis. CR for non-target lesion: Disappearance of all extranodal non-target lesions, all lymph nodes must be non-pathological in size (<10mm short axis) and norrmalization of tumor marker level. PR: at least a 30% decrease in the SLD of target lesions, taking as reference the baseline sum diameters. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD). PD was defined as at least a 20% increase in the sum of diameters of target lesions.
Time Frame Screening, at 8-week intervals thereafter (on Day 1 of every odd-numbered Cycle of 28-days) through 15 Cycles and every 3 Cycles thereafter until disease progression or up to end of the study (approximately up to 69 months)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population included all participants who were randomized to each regimen regardless of whether they received study drug or adhered to the assigned dose.
Arm/Group Title Brigatinib 90 mg Brigatinib 90 mg - 180 mg
Hide Arm/Group Description:
Brigatinib 90 mg, tablets, orally, once daily in each Cycle of 28 days until disease progression or intolerable toxicity (median duration of exposure was 402 days).
Brigatinib 90 mg, tablets, orally, once daily for 7 days followed by brigatinib 180 mg, orally once daily in Cycle 1 of 28 days followed by brigatinib 180 mg, orally once daily in Cycle 2 and onward Cycles of 28 days until disease progression or intolerable toxicity (median duration of exposure was 522 days).
Overall Number of Participants Analyzed 112 110
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
81.3
(72.8 to 88.0)
86.4
(78.5 to 92.2)
10.Secondary Outcome
Title Progression Free Survival (PFS)
Hide Description PFS was defined as the time interval from the date of the first dose of the study treatment until the first date at which disease progression is objectively documented, or death due to any cause, whichever occurs first. Disease progression for target lesion: SLD increased by at least 20% from the smallest value on study (including Baseline, if that is the smallest) and SLD must also demonstrate an absolute increase of at least 5 mm or development of any new lesion. Disease progression for non-target lesion: Unequivocal progression of existing non-target lesions. (Subjective judgment by experienced reader). The analysis was based on the Kaplan-Meier (KM) Estimates.
Time Frame Up to approximately 69 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population included all participants who were randomized to each regimen regardless of whether they received study drug or adhered to the assigned dose.
Arm/Group Title Brigatinib 90 mg Brigatinib 90 mg - 180 mg
Hide Arm/Group Description:
Brigatinib 90 mg, tablets, orally, once daily in each Cycle of 28 days until disease progression or intolerable toxicity (median duration of exposure was 402 days).
Brigatinib 90 mg, tablets, orally, once daily for 7 days followed by brigatinib 180 mg, orally once daily in Cycle 1 of 28 days followed by brigatinib 180 mg, orally once daily in Cycle 2 and onward Cycles of 28 days until disease progression or intolerable toxicity (median duration of exposure was 522 days).
Overall Number of Participants Analyzed 112 110
Median (95% Confidence Interval)
Unit of Measure: months
9.2
(7.4 to 11.1)
15.6
(11.1 to 18.5)
11.Secondary Outcome
Title Overall Survival (OS)
Hide Description OS is defined as the time interval from the date of the first dose of the study treatment until death due to any cause. Intracranial OS was calculated by Kaplan-Meier estimation.
Time Frame Up to approximately 69 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population included all participants who were randomized to each regimen regardless of whether they received study drug or adhered to the assigned dose.
Arm/Group Title Brigatinib 90 mg Brigatinib 90 mg - 180 mg
Hide Arm/Group Description:
Brigatinib 90 mg, tablets, orally, once daily in each Cycle of 28 days until disease progression or intolerable toxicity (median duration of exposure was 402 days).
Brigatinib 90 mg, tablets, orally, once daily for 7 days followed by brigatinib 180 mg, orally once daily in Cycle 1 of 28 days followed by brigatinib 180 mg, orally once daily in Cycle 2 and onward Cycles of 28 days until disease progression or intolerable toxicity (median duration of exposure was 522 days).
Overall Number of Participants Analyzed 112 110
Median (95% Confidence Interval)
Unit of Measure: months
25.9
(18.2 to 45.8)
40.6 [1] 
(32.5 to NA)
[1]
Upper limit of 95% confidence interval was not estimable due to low number of participants with event.
12.Secondary Outcome
Title Number of Participants Who Had at Least One Treatment-Emergent Adverse Event (TEAE)
Hide Description An Adverse Event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A TEAE was defined as an adverse event with an onset that occurs after receiving study drug.
Time Frame From first dose of study drug up to 30 days following the last dose of study drug (approximately up to 69 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population included all participants who received at least one dose of study drug.
Arm/Group Title Brigatinib 90 mg Brigatinib 90 mg - 180 mg
Hide Arm/Group Description:
Brigatinib 90 mg, tablets, orally, once daily in each Cycle of 28 days until disease progression or intolerable toxicity (median duration of exposure was 402 days).
Brigatinib 90 mg, tablets, orally, once daily for 7 days followed by brigatinib 180 mg, orally once daily in Cycle 1 of 28 days followed by brigatinib 180 mg, orally once daily in Cycle 2 and onward Cycles of 28 days until disease progression or intolerable toxicity (median duration of exposure was 522 days).
Overall Number of Participants Analyzed 109 110
Measure Type: Number
Unit of Measure: participants
109 110
13.Secondary Outcome
Title Pre-dose Brigatinib Plasma Concentration
Hide Description [Not Specified]
Time Frame Day 1 Cycles 2, 3, 4 and 5 (each Cycle of 28-days) pre-dose
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population included all participants who were randomized to each regimen regardless of whether they received study drug or adhered to the assigned dose. Here, number of participants analyzed is the participants who were evaluable for this outcome measure.
Arm/Group Title Brigatinib 90 mg Brigatinib 90 mg - 180 mg
Hide Arm/Group Description:
Brigatinib 90 mg, tablets, orally, once daily in each Cycle of 28 days until disease progression or intolerable toxicity (median duration of exposure was 402 days).
Brigatinib 90 mg, tablets, orally, once daily for 7 days followed by brigatinib 180 mg, orally once daily in Cycle 1 of 28 days followed by brigatinib 180 mg, orally once daily in Cycle 2 and onward Cycles of 28 days until disease progression or intolerable toxicity (median duration of exposure was 522 days).
Overall Number of Participants Analyzed 112 110
Mean (Standard Deviation)
Unit of Measure: ng/ml
Cycle 2 Number Analyzed 101 participants 97 participants
295.2  (252.0) 520.0  (321.9)
Cycle 3 Number Analyzed 91 participants 92 participants
263.9  (238.9) 537.0  (360.3)
Cycle 4 Number Analyzed 80 participants 87 participants
236.1  (188.0) 564.7  (415.0)
Cycle 5 Number Analyzed 80 participants 79 participants
256.4  (282.3) 579.7  (396.7)
14.Secondary Outcome
Title Patient-reported Symptoms Global Health Status/Quality of Life (QoL) Scores
Hide Description Patient-reported symptoms global health status/quality of life (QoL) scores were based on questions 29 and 30 of the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-C30 (QLQ-C30). The first 28 questions used 4-point scale (1=not at all,2=a little,3=quite a bit,4=very much) for evaluating 5 functional scales (physical, role, cognitive, emotional, and social functioning); 3 symptom scales (fatigue, pain, and nausea/vomiting); and last 2 questions on global health status/QoL scale are coded on 7-point scale (1=very poor to 7=excellent). Six single-item scales also are included (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Raw scores for multi-item scales and single-item measures was linearly transformed to obtain the score ranging from 0 to 100, where higher score represents a higher ("better") level of functioning.
Time Frame Baseline and at each 28-day cycle up to end of the study (up to approximately 69 months)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population included all participants who were randomized to each regimen regardless of whether they received study drug or adhered to the assigned dose. Here, number of participants analyzed is the participants who were evaluable for this outcome measure.
Arm/Group Title Brigatinib 90 mg Brigatinib 90 mg - 180 mg
Hide Arm/Group Description:
Brigatinib 90 mg, tablets, orally, once daily in each Cycle of 28 days until disease progression or intolerable toxicity (median duration of exposure was 402 days).
Brigatinib 90 mg, tablets, orally, once daily for 7 days followed by brigatinib 180 mg, orally once daily in Cycle 1 of 28 days followed by brigatinib 180 mg, orally once daily in Cycle 2 and onward Cycles of 28 days until disease progression or intolerable toxicity (median duration of exposure was 522 days).
Overall Number of Participants Analyzed 112 110
Mean (Standard Deviation)
Unit of Measure: unit on a scale
Baseline Number Analyzed 108 participants 108 participants
52.39  (27.42) 58.49  (23.40)
Cycle 2 Number Analyzed 101 participants 97 participants
64.19  (20.73) 65.72  (19.54)
Cycle 3 Number Analyzed 91 participants 91 participants
65.57  (24.06) 68.50  (20.52)
Cycle 4 Number Analyzed 84 participants 89 participants
69.44  (20.59) 66.95  (20.89)
Cycle 5 Number Analyzed 82 participants 85 participants
70.12  (20.28) 71.86  (17.63)
Cycle 6 Number Analyzed 79 participants 82 participants
70.15  (20.18) 71.24  (18.66)
Cycle 7 Number Analyzed 77 participants 80 participants
67.42  (20.29) 70.21  (21.66)
Cycle 8 Number Analyzed 73 participants 78 participants
67.24  (22.79) 69.87  (20.42)
Cycle 9 Number Analyzed 70 participants 75 participants
68.45  (22.61) 68.67  (21.35)
Cycle 10 Number Analyzed 65 participants 70 participants
71.79  (20.61) 67.98  (23.25)
Cycle 11 Number Analyzed 61 participants 70 participants
72.54  (19.56) 68.45  (21.37)
Cycle 12 Number Analyzed 61 participants 65 participants
68.03  (23.08) 70.51  (21.35)
Cycle 13 Number Analyzed 58 participants 64 participants
70.11  (19.93) 72.79  (19.20)
Cycle 14 Number Analyzed 55 participants 57 participants
69.55  (20.04) 70.76  (19.42)
Cycle 15 Number Analyzed 54 participants 58 participants
70.06  (21.08) 70.83  (20.66)
Cycle 16 Number Analyzed 50 participants 58 participants
68.17  (22.94) 72.27  (18.36)
Cycle 17 Number Analyzed 48 participants 61 participants
73.61  (18.78) 69.81  (20.36)
Cycle 18 Number Analyzed 43 participants 58 participants
67.64  (22.80) 71.55  (17.94)
Cycle 19 Number Analyzed 43 participants 55 participants
69.57  (23.14) 72.12  (20.49)
Cycle 20 Number Analyzed 40 participants 52 participants
66.04  (24.05) 72.76  (18.53)
Cycle 21 Number Analyzed 39 participants 50 participants
69.23  (22.87) 69.83  (19.04)
Cycle 22 Number Analyzed 36 participants 46 participants
72.69  (21.70) 71.20  (18.90)
Cycle 23 Number Analyzed 35 participants 47 participants
72.38  (21.93) 71.10  (20.10)
Cycle 24 Number Analyzed 32 participants 42 participants
72.66  (19.66) 71.43  (15.74)
Cycle 25 Number Analyzed 34 participants 39 participants
71.57  (21.72) 70.09  (19.38)
Cycle 26 Number Analyzed 32 participants 36 participants
71.88  (22.28) 69.68  (20.43)
Cycle 27 Number Analyzed 33 participants 36 participants
71.46  (20.94) 70.83  (21.96)
Cycle 28 Number Analyzed 31 participants 37 participants
71.24  (22.24) 69.59  (20.24)
Cycle 29 Number Analyzed 30 participants 37 participants
70.00  (21.73) 71.17  (22.27)
Cycle 30 Number Analyzed 29 participants 34 participants
69.25  (21.72) 70.83  (18.03)
Cycle 31 Number Analyzed 26 participants 33 participants
75.64  (17.63) 69.95  (18.15)
Cycle 32 Number Analyzed 25 participants 31 participants
73.00  (20.02) 70.97  (20.28)
Cycle 33 Number Analyzed 25 participants 32 participants
71.67  (20.41) 70.31  (20.84)
Cycle 34 Number Analyzed 21 participants 31 participants
72.62  (20.61) 69.62  (20.70)
Cycle 35 Number Analyzed 21 participants 31 participants
72.22  (18.88) 66.67  (22.97)
Cycle 36 Number Analyzed 20 participants 30 participants
68.33  (22.72) 71.67  (19.89)
Cycle 37 Number Analyzed 20 participants 30 participants
73.33  (19.42) 72.50  (19.47)
Cycle 38 Number Analyzed 18 participants 29 participants
68.98  (22.10) 72.99  (17.49)
Cycle 39 Number Analyzed 17 participants 26 participants
68.63  (25.09) 73.72  (19.96)
Cycle 40 Number Analyzed 17 participants 26 participants
71.57  (24.13) 69.87  (23.10)
Cycle 41 Number Analyzed 17 participants 26 participants
72.55  (21.20) 68.27  (22.98)
Cycle 42 Number Analyzed 17 participants 24 participants
72.06  (21.84) 72.57  (20.78)
Cycle 43 Number Analyzed 17 participants 23 participants
67.65  (24.63) 71.01  (22.17)
Cycle 44 Number Analyzed 17 participants 22 participants
72.55  (20.57) 73.48  (19.35)
Cycle 45 Number Analyzed 14 participants 22 participants
66.67  (19.88) 72.35  (22.03)
Cycle 46 Number Analyzed 15 participants 22 participants
70.56  (19.12) 71.59  (20.52)
Cycle 47 Number Analyzed 14 participants 21 participants
60.12  (25.36) 73.02  (19.88)
Cycle 48 Number Analyzed 13 participants 21 participants
65.38  (20.93) 74.60  (19.80)
Cycle 49 Number Analyzed 13 participants 20 participants
57.69  (24.88) 71.67  (22.69)
Cycle 50 Number Analyzed 13 participants 20 participants
61.54  (26.47) 70.00  (24.54)
Cycle 51 Number Analyzed 12 participants 21 participants
63.19  (23.96) 69.05  (22.69)
Cycle 52 Number Analyzed 12 participants 21 participants
56.94  (22.71) 72.22  (22.26)
Cycle 53 Number Analyzed 12 participants 20 participants
61.11  (21.42) 70.83  (23.02)
Cycle 54 Number Analyzed 12 participants 19 participants
61.81  (25.24) 71.49  (20.47)
Cycle 55 Number Analyzed 10 participants 19 participants
63.33  (26.12) 72.37  (20.42)
Cycle 56 Number Analyzed 9 participants 18 participants
63.89  (23.94) 73.61  (19.23)
Cycle 57 Number Analyzed 10 participants 17 participants
65.00  (19.95) 73.53  (19.37)
Cycle 58 Number Analyzed 10 participants 14 participants
65.00  (25.09) 70.83  (20.61)
Cycle 59 Number Analyzed 9 participants 14 participants
64.81  (25.27) 71.43  (19.81)
Cycle 60 Number Analyzed 8 participants 9 participants
70.83  (27.82) 73.15  (19.44)
Cycle 61 Number Analyzed 7 participants 8 participants
71.43  (28.41) 78.13  (19.89)
Cycle 62 Number Analyzed 5 participants 7 participants
66.67  (23.57) 79.76  (15.85)
Cycle 63 Number Analyzed 4 participants 7 participants
58.33  (31.91) 78.57  (17.91)
Cycle 64 Number Analyzed 3 participants 7 participants
61.11  (34.69) 77.38  (20.81)
Cycle 65 Number Analyzed 2 participants 6 participants
75.00  (35.36) 76.39  (22.62)
Cycle 66 Number Analyzed 2 participants 4 participants
75.00  (35.36) 77.08  (31.46)
Cycle 67 Number Analyzed 2 participants 1 participants
75.00  (35.36) 41.67 [1]   (NA)
Cycle 68 Number Analyzed 0 participants 1 participants
41.67 [2]   (NA)
Cycle 69 Number Analyzed 0 participants 1 participants
58.33 [2]   (NA)
Cycle 70 Number Analyzed 0 participants 1 participants
41.67 [2]   (NA)
Cycle 71 Number Analyzed 0 participants 1 participants
41.67 [2]   (NA)
Cycle 72 Number Analyzed 0 participants 1 participants
75.00 [2]   (NA)
End of Treatment Number Analyzed 80 participants 68 participants
52.29  (28.25) 61.15  (23.15)
Follow-Up 30 Days After Last Dose Number Analyzed 43 participants 45 participants
61.05  (30.58) 61.67  (23.33)
[1]
Standard deviation (SD) was not evaluable for 1 participant.
[2]
SD was not evaluable for 1 participant.
Time Frame All-cause Mortality: From first dose of study drug up to end of the study (approximately up to 69 months); Serious and Other Adverse Events: From first dose of study drug up to 30 days following the last dose of study drug (approximately up to 69 months)
Adverse Event Reporting Description At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
 
Arm/Group Title Brigatinib 90 mg Brigatinib 90 mg - 180 mg
Hide Arm/Group Description Brigatinib 90 mg, tablets, orally, once daily in each Cycle of 28 days until disease progression or intolerable toxicity (median duration of exposure was 402 days). Brigatinib 90 mg, tablets, orally, once daily for 7 days followed by brigatinib 180 mg, orally once daily in Cycle 1 of 28 days followed by brigatinib 180 mg, orally once daily in Cycle 2 and onward Cycles of 28 days until disease progression or intolerable toxicity (median duration of exposure was 522 days).
All-Cause Mortality
Brigatinib 90 mg Brigatinib 90 mg - 180 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   64/109 (58.72%)   54/110 (49.09%) 
Hide Serious Adverse Events
Brigatinib 90 mg Brigatinib 90 mg - 180 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   58/109 (53.21%)   69/110 (62.73%) 
Blood and lymphatic system disorders     
Lymph node pain  1  1/109 (0.92%)  0/110 (0.00%) 
Anaemia  1  1/109 (0.92%)  1/110 (0.91%) 
Cardiac disorders     
Atrial fibrillation  1  1/109 (0.92%)  1/110 (0.91%) 
Angina pectoris  1  0/109 (0.00%)  1/110 (0.91%) 
Supraventricular tachycardia  1  0/109 (0.00%)  1/110 (0.91%) 
Ear and labyrinth disorders     
Vertigo positional  1  2/109 (1.83%)  0/110 (0.00%) 
Eye disorders     
Macular oedema  1  0/109 (0.00%)  1/110 (0.91%) 
Gastrointestinal disorders     
Abdominal pain  1  1/109 (0.92%)  1/110 (0.91%) 
Diarrhoea  1  1/109 (0.92%)  0/110 (0.00%) 
Food poisoning  1  0/109 (0.00%)  1/110 (0.91%) 
Gastrointestinal haemorrhage  1  1/109 (0.92%)  0/110 (0.00%) 
Small intestinal obstruction  1  1/109 (0.92%)  0/110 (0.00%) 
Abdominal pain upper†  1  2/109 (1.83%)  0/110 (0.00%) 
Dysphagia  1  1/109 (0.92%)  0/110 (0.00%) 
Haematemesis  1  1/109 (0.92%)  0/110 (0.00%) 
Haematochezia  1  0/109 (0.00%)  1/110 (0.91%) 
Tooth socket haemorrhage  1  0/109 (0.00%)  1/110 (0.91%) 
General disorders     
Asthenia  1  1/109 (0.92%)  0/110 (0.00%) 
Infusion site thrombosis  1  0/109 (0.00%)  1/110 (0.91%) 
Sudden death  1  0/109 (0.00%)  1/110 (0.91%) 
Euthanasia  1  0/109 (0.00%)  1/110 (0.91%) 
Non-cardiac chest pain  1  1/109 (0.92%)  0/110 (0.00%) 
Oedema peripheral  1  1/109 (0.92%)  0/110 (0.00%) 
Pyrexia  1  0/109 (0.00%)  1/110 (0.91%) 
General physical health deterioration  1  1/109 (0.92%)  1/110 (0.91%) 
Hepatobiliary disorders     
Cholangitis acute  1  1/109 (0.92%)  0/110 (0.00%) 
Jaundice cholestatic  1  0/109 (0.00%)  1/110 (0.91%) 
Hepatic function abnormal†  1  0/109 (0.00%)  2/110 (1.82%) 
Infections and infestations     
Pneumonia  1  4/109 (3.67%)  13/110 (11.82%) 
Appendicitis  1  1/109 (0.92%)  2/110 (1.82%) 
Bronchitis  1  2/109 (1.83%)  1/110 (0.91%) 
Atypical pneumonia  1  1/109 (0.92%)  0/110 (0.00%) 
Cellulitis  1  0/109 (0.00%)  1/110 (0.91%) 
Meningitis bacterial  1  1/109 (0.92%)  1/110 (0.91%) 
Tuberculous pleurisy  1  0/109 (0.00%)  1/110 (0.91%) 
Urosepsis  1  1/109 (0.92%)  1/110 (0.91%) 
Bronchopulmonary aspergillosis  1  0/109 (0.00%)  1/110 (0.91%) 
Clostridium difficile colitis  1  0/109 (0.00%)  1/110 (0.91%) 
Diverticulitis  1  0/109 (0.00%)  1/110 (0.91%) 
Escherichia urinary tract infection  1  0/109 (0.00%)  1/110 (0.91%) 
Haematoma infection  1  1/109 (0.92%)  0/110 (0.00%) 
Peritonitis  1  1/109 (0.92%)  0/110 (0.00%) 
Pyelonephritis  1  0/109 (0.00%)  1/110 (0.91%) 
Skin infection  1  0/109 (0.00%)  1/110 (0.91%) 
Injury, poisoning and procedural complications     
Head injury  1  0/109 (0.00%)  1/110 (0.91%) 
Radiation necrosis  1  0/109 (0.00%)  1/110 (0.91%) 
Radiation pneumonitis  1  0/109 (0.00%)  1/110 (0.91%) 
Fall  1  1/109 (0.92%)  0/110 (0.00%) 
Hip fracture  1  0/109 (0.00%)  1/110 (0.91%) 
Skin laceration  1  1/109 (0.92%)  0/110 (0.00%) 
Investigations     
Neutrophil count decreased  1  0/109 (0.00%)  1/110 (0.91%) 
Platelet count decreased  1  1/109 (0.92%)  0/110 (0.00%) 
Metabolism and nutrition disorders     
Dehydration  1  2/109 (1.83%)  0/110 (0.00%) 
Hyponatraemia  1  0/109 (0.00%)  1/110 (0.91%) 
Decreased appetite  1  0/109 (0.00%)  1/110 (0.91%) 
Hyperglycaemia  1  0/109 (0.00%)  1/110 (0.91%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  1/109 (0.92%)  1/110 (0.91%) 
Arthralgia  1  1/109 (0.92%)  0/110 (0.00%) 
Neck pain  1  1/109 (0.92%)  0/110 (0.00%) 
Pathological fracture  1  1/109 (0.92%)  0/110 (0.00%) 
Osteoarthritis  1  1/109 (0.92%)  1/110 (0.91%) 
Pain in extremity  1  1/109 (0.92%)  1/110 (0.91%) 
Muscular weakness  1  1/109 (0.92%)  0/110 (0.00%) 
Musculoskeletal pain  1  0/109 (0.00%)  1/110 (0.91%) 
Osteonecrosis  1  0/109 (0.00%)  1/110 (0.91%) 
Soft tissue necrosis  1  1/109 (0.92%)  0/110 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Neoplasm progression  1  15/109 (13.76%)  8/110 (7.27%) 
Malignant pleural effusion  1  2/109 (1.83%)  4/110 (3.64%) 
Metastases to central nervous system  1  0/109 (0.00%)  3/110 (2.73%) 
Metastases to meninges  1  1/109 (0.92%)  0/110 (0.00%) 
Squamous cell carcinoma of skin  1  1/109 (0.92%)  1/110 (0.91%) 
Bowens disease  1  0/109 (0.00%)  1/110 (0.91%) 
Metastases to peritoneum  1  1/109 (0.92%)  0/110 (0.00%) 
Metastatic malignant melanoma  1  1/109 (0.92%)  0/110 (0.00%) 
Thyroid cancer  1  1/109 (0.92%)  0/110 (0.00%) 
Tumour associated fever  1  1/109 (0.92%)  0/110 (0.00%) 
Metastases to liver  1  1/109 (0.92%)  0/110 (0.00%) 
Nervous system disorders     
Epilepsy  1  3/109 (2.75%)  1/110 (0.91%) 
Cerebrovascular accident  1  1/109 (0.92%)  0/110 (0.00%) 
Generalised tonic-clonic seizure  1  1/109 (0.92%)  0/110 (0.00%) 
Headache  1  1/109 (0.92%)  0/110 (0.00%) 
Nervous system disorder  1  0/109 (0.00%)  1/110 (0.91%) 
Seizure  1  4/109 (3.67%)  1/110 (0.91%) 
Simple partial seizures  1  0/109 (0.00%)  1/110 (0.91%) 
Spinal cord compression  1  1/109 (0.92%)  0/110 (0.00%) 
Syncope  1  1/109 (0.92%)  2/110 (1.82%) 
Transient ischaemic attack  1  1/109 (0.92%)  1/110 (0.91%) 
Hemiparesis  1  1/109 (0.92%)  1/110 (0.91%) 
Aphasia  1  1/109 (0.92%)  0/110 (0.00%) 
Cognitive disorder  1  0/109 (0.00%)  1/110 (0.91%) 
Dizziness  1  1/109 (0.92%)  0/110 (0.00%) 
Hyperaesthesia  1  1/109 (0.92%)  0/110 (0.00%) 
Intracranial pressure increased  1  1/109 (0.92%)  0/110 (0.00%) 
Paraesthesia  1  0/109 (0.00%)  1/110 (0.91%) 
Tonic clonic movements  1  1/109 (0.92%)  0/110 (0.00%) 
Product Issues     
Device occlusion  1  1/109 (0.92%)  1/110 (0.91%) 
Psychiatric disorders     
Confusional state  1  2/109 (1.83%)  2/110 (1.82%) 
Renal and urinary disorders     
Hydronephrosis  1  2/109 (1.83%)  0/110 (0.00%) 
Renal impairment  1  1/109 (0.92%)  0/110 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Pneumonitis  1  3/109 (2.75%)  10/110 (9.09%) 
Dyspnoea  1  3/109 (2.75%)  5/110 (4.55%) 
Pulmonary embolism  1  1/109 (0.92%)  2/110 (1.82%) 
Dyspnoea exertional  1  1/109 (0.92%)  0/110 (0.00%) 
Haemoptysis  1  0/109 (0.00%)  2/110 (1.82%) 
Respiratory failure  1  1/109 (0.92%)  0/110 (0.00%) 
Oesophagobronchial fistula  1  1/109 (0.92%)  0/110 (0.00%) 
Pleural effusion  1  1/109 (0.92%)  0/110 (0.00%) 
Pneumonia aspiration  1  1/109 (0.92%)  0/110 (0.00%) 
Pneumothorax  1  1/109 (0.92%)  0/110 (0.00%) 
Skin and subcutaneous tissue disorders     
Angioedema  1  0/109 (0.00%)  1/110 (0.91%) 
Dermatitis allergic  1  0/109 (0.00%)  1/110 (0.91%) 
Paraneoplastic dermatomyositis  1  0/109 (0.00%)  1/110 (0.91%) 
Rash erythematous  1  1/109 (0.92%)  0/110 (0.00%) 
Vascular disorders     
Behcets syndrome  1  0/109 (0.00%)  1/110 (0.91%) 
Hypertension  1  0/109 (0.00%)  1/110 (0.91%) 
Iliac artery stenosis  1  0/109 (0.00%)  1/110 (0.91%) 
1
Term from vocabulary, MedDRA 23.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Brigatinib 90 mg Brigatinib 90 mg - 180 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   108/109 (99.08%)   105/110 (95.45%) 
Blood and lymphatic system disorders     
Anaemia  1  8/109 (7.34%)  8/110 (7.27%) 
Cardiac disorders     
Palpitations  1  1/109 (0.92%)  6/110 (5.45%) 
Ear and labyrinth disorders     
Vertigo  1  3/109 (2.75%)  13/110 (11.82%) 
Eye disorders     
Vision blurred  1  7/109 (6.42%)  9/110 (8.18%) 
Gastrointestinal disorders     
Nausea  1  47/109 (43.12%)  55/110 (50.00%) 
Diarrhoea  1  34/109 (31.19%)  51/110 (46.36%) 
Vomiting  1  44/109 (40.37%)  39/110 (35.45%) 
Constipation  1  29/109 (26.61%)  28/110 (25.45%) 
Abdominal pain  1  13/109 (11.93%)  10/110 (9.09%) 
Dyspepsia  1  8/109 (7.34%)  8/110 (7.27%) 
Stomatitis  1  5/109 (4.59%)  10/110 (9.09%) 
Dry mouth  1  4/109 (3.67%)  11/110 (10.00%) 
Abdominal pain upper  1  11/109 (10.09%)  13/110 (11.82%) 
General disorders     
Pyrexia  1  23/109 (21.10%)  11/110 (10.00%) 
Asthenia  1  16/109 (14.68%)  19/110 (17.27%) 
Oedema peripheral  1  13/109 (11.93%)  14/110 (12.73%) 
Fatigue  1  34/109 (31.19%)  41/110 (37.27%) 
Influenza like illness  1  8/109 (7.34%)  9/110 (8.18%) 
Non-cardiac chest pain  1  6/109 (5.50%)  5/110 (4.55%) 
Infections and infestations     
Nasopharyngitis  1  15/109 (13.76%)  15/110 (13.64%) 
Upper respiratory tract infection  1  13/109 (11.93%)  10/110 (9.09%) 
Urinary tract infection  1  9/109 (8.26%)  13/110 (11.82%) 
Pneumonia  1  3/109 (2.75%)  15/110 (13.64%) 
Bronchitis  1  5/109 (4.59%)  6/110 (5.45%) 
Sinusitis  1  3/109 (2.75%)  8/110 (7.27%) 
Herpes zoster  1  1/109 (0.92%)  6/110 (5.45%) 
Injury, poisoning and procedural complications     
Fall  1  2/109 (1.83%)  7/110 (6.36%) 
Investigations     
Blood creatine phosphokinase increased  1  24/109 (22.02%)  41/110 (37.27%) 
Amylase increased  1  16/109 (14.68%)  20/110 (18.18%) 
Aspartate aminotransferase increased  1  15/109 (13.76%)  22/110 (20.00%) 
Lipase increased  1  15/109 (13.76%)  23/110 (20.91%) 
Alanine aminotransferase increased  1  15/109 (13.76%)  18/110 (16.36%) 
Blood lactate dehydrogenase increased  1  3/109 (2.75%)  10/110 (9.09%) 
Weight decreased  1  8/109 (7.34%)  7/110 (6.36%) 
Blood alkaline phosphatase increased  1  7/109 (6.42%)  6/110 (5.45%) 
Blood creatinine increased  1  5/109 (4.59%)  8/110 (7.27%) 
Electrocardiogram QT prolonged  1  4/109 (3.67%)  8/110 (7.27%) 
Metabolism and nutrition disorders     
Decreased appetite  1  32/109 (29.36%)  27/110 (24.55%) 
Hyperglycaemia  1  6/109 (5.50%)  9/110 (8.18%) 
Hypokalaemia  1  7/109 (6.42%)  6/110 (5.45%) 
Hyponatraemia  1  5/109 (4.59%)  8/110 (7.27%) 
Musculoskeletal and connective tissue disorders     
Muscle spasms  1  17/109 (15.60%)  28/110 (25.45%) 
Arthralgia  1  19/109 (17.43%)  21/110 (19.09%) 
Back pain  1  16/109 (14.68%)  30/110 (27.27%) 
Pain in extremity  1  17/109 (15.60%)  15/110 (13.64%) 
Myalgia  1  7/109 (6.42%)  17/110 (15.45%) 
Musculoskeletal chest pain  1  7/109 (6.42%)  10/110 (9.09%) 
Neck pain  1  4/109 (3.67%)  13/110 (11.82%) 
Musculoskeletal pain  1  9/109 (8.26%)  15/110 (13.64%) 
Muscular weakness  1  6/109 (5.50%)  4/110 (3.64%) 
Nervous system disorders     
Headache  1  39/109 (35.78%)  44/110 (40.00%) 
Dizziness  1  18/109 (16.51%)  22/110 (20.00%) 
Paraesthesia  1  13/109 (11.93%)  12/110 (10.91%) 
Peripheral sensory neuropathy  1  8/109 (7.34%)  10/110 (9.09%) 
Memory impairment  1  4/109 (3.67%)  11/110 (10.00%) 
Seizure  1  4/109 (3.67%)  11/110 (10.00%) 
Hypoaesthesia  1  5/109 (4.59%)  6/110 (5.45%) 
Cognitive disorder  1  3/109 (2.75%)  6/110 (5.45%) 
Tremor  1  2/109 (1.83%)  6/110 (5.45%) 
Psychiatric disorders     
Insomnia  1  20/109 (18.35%)  15/110 (13.64%) 
Anxiety  1  3/109 (2.75%)  11/110 (10.00%) 
Renal and urinary disorders     
Haematuria  1  3/109 (2.75%)  9/110 (8.18%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  35/109 (32.11%)  45/110 (40.91%) 
Dyspnoea  1  28/109 (25.69%)  31/110 (28.18%) 
Oropharyngeal pain  1  12/109 (11.01%)  11/110 (10.00%) 
Dysphonia  1  8/109 (7.34%)  7/110 (6.36%) 
Productive cough  1  10/109 (9.17%)  9/110 (8.18%) 
Dyspnoea exertional  1  6/109 (5.50%)  2/110 (1.82%) 
Haemoptysis  1  4/109 (3.67%)  8/110 (7.27%) 
Epistaxis  1  4/109 (3.67%)  8/110 (7.27%) 
Skin and subcutaneous tissue disorders     
Rash  1  6/109 (5.50%)  4/110 (3.64%) 
Pruritus  1  12/109 (11.01%)  15/110 (13.64%) 
Dermatitis acneiform  1  7/109 (6.42%)  4/110 (3.64%) 
Rash erythematous  1  9/109 (8.26%)  14/110 (12.73%) 
Dry skin  1  8/109 (7.34%)  3/110 (2.73%) 
Rash maculo-papular  1  3/109 (2.75%)  7/110 (6.36%) 
Rash pruritic  1  2/109 (1.83%)  8/110 (7.27%) 
Vascular disorders     
Hypertension  1  21/109 (19.27%)  35/110 (31.82%) 
1
Term from vocabulary, MedDRA 23.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Director
Organization: Takeda
Phone: +1-877-825-3327
EMail: trialdisclosures@takeda.com
Layout table for additonal information
Responsible Party: Takeda ( Ariad Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT02094573    
Other Study ID Numbers: AP26113-13-201
2013-002134-21 ( EudraCT Number )
U1111-1196-8246 ( Other Identifier: WHO )
First Submitted: March 18, 2014
First Posted: March 24, 2014
Results First Submitted: May 26, 2017
Results First Posted: June 21, 2017
Last Update Posted: March 15, 2021