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    Clinical Trial Results:
    Brigatinib in Patients With Anaplastic Lymphoma Kinase-Positive (ALK+), Advanced Non–Small-Cell Lung Cancer (NSCLC) Progressed on Alectinib or Ceritinib

    Summary
    EudraCT number
    		 2018-000635-27
    Trial protocol
    		 SE   DE   ES   AT   NL   IT  
    Global end of trial date
    21 Aug 2024

    Results information
    Results version number
    		 v1(current)
    This version publication date
    26 Jun 2025
    First version publication date
    26 Jun 2025
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    Brigatinib-2002
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03535740
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Takeda
    Sponsor organisation address
    95 Hayden Ave, Lexington, MA, United States, 02421
    Public contact
    Study Director, Takeda, TrialDisclosures@takeda.com
    Scientific contact
    Study Director, Takeda, TrialDisclosures@takeda.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
    Final
    Date of interim/final analysis
    21 Aug 2024
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    21 Aug 2024
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The main aim of this study is to determine the efficacy of brigatinib in participants with ALK+ locally advanced or metastatic NSCLC whose disease has progressed on therapy with alectinib or ceritinib.
    Protection of trial subjects
    Each participant signed an informed consent form (ICF) before participating in the study.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    31 Jan 2019
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Canada: 6
    Country: Number of subjects enrolled
    United States: 7
    Country: Number of subjects enrolled
    Austria: 1
    Country: Number of subjects enrolled
    France: 7
    Country: Number of subjects enrolled
    Germany: 3
    Country: Number of subjects enrolled
    Italy: 16
    Country: Number of subjects enrolled
    Netherlands: 2
    Country: Number of subjects enrolled
    Spain: 11
    Country: Number of subjects enrolled
    Sweden: 2
    Country: Number of subjects enrolled
    China: 14
    Country: Number of subjects enrolled
    Hong Kong: 6
    Country: Number of subjects enrolled
    Japan: 3
    Country: Number of subjects enrolled
    Korea, Republic of: 20
    Country: Number of subjects enrolled
    Taiwan: 4
    Country: Number of subjects enrolled
    Australia: 1
    Worldwide total number of subjects
    103
    EEA total number of subjects
    42
    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)
    80
    From 65 to 84 years
    23
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 Participants took part in the study at 54 investigative sites in Canada, United States, Austria, France, Germany, Italy, Netherlands, Spain, Sweden, China, Hong Kong, Japan, Korea, Taiwan, and Australia from 31 January 2019 to 21 August 2024.

    Pre-assignment
    Screening details
    		 Subjects with ALK+,advanced NSCLC were enrolled to receive brigatinib 90mg followed by 180mg up to disease progression.102 subjects discontinued study upto interim data cut-off date:20 May 2021,by then all study outcome measures were met&data collection was complete.1 subject stayed on until study completion as mean to provide access to brigatinib.

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

    Arms
    Arm title
    		 Brigatinib 90 mg/180mg With Optional Dose Escalation to 240 mg
    Arm description
    		 Participants received brigatinib 90 mg, tablets, orally, once daily (QD) for 7 days, followed by brigatinib 180 mg, tablets, orally, QD for until objective disease progression per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, as assessed by the investigator, or intolerable toxicity. Participants who experienced progression on the 180 mg dose and had not experienced toxicities greater than Grade 2 had the option to receive brigatinib 240 mg QD based on investigator’s discretion, up to 28 months from start of enrollment until data cut-off: 20 May 2021.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Brigatinib
    Investigational medicinal product code
    Brigatinib-2002
    Other name
    AP26113
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received brigatinib 90 mg, tablets, orally, once daily for 7 days, followed by brigatinib 180 mg, tablets, orally, once daily.

    Number of subjects in period 1
    		Brigatinib 90 mg/180mg With Optional Dose Escalation to 240 mg
    Started
    103
    Participants who receivedbrigatinib240mg
    13
    Completed
    0
    Not completed
    103
         Adverse event, serious fatal
    44
         Consent withdrawn by subject
    13
         Site Terminated by Sponsor
    45
         Lost to follow-up
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Brigatinib 90 mg/180mg With Optional Dose Escalation to 240 mg
    Reporting group description
    		 Participants received brigatinib 90 mg, tablets, orally, once daily (QD) for 7 days, followed by brigatinib 180 mg, tablets, orally, QD for until objective disease progression per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, as assessed by the investigator, or intolerable toxicity. Participants who experienced progression on the 180 mg dose and had not experienced toxicities greater than Grade 2 had the option to receive brigatinib 240 mg QD based on investigator’s discretion, up to 28 months from start of enrollment until data cut-off: 20 May 2021.

    Reporting group values
    		 Brigatinib 90 mg/180mg With Optional Dose Escalation to 240 mg Total
    Number of subjects
    		 103
    Age Categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 54.7 ( 11.94 ) -
    Gender categorical
    Units: Subjects
        Male
    		 51 51
        Female
    		 52 52
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 2 2
        Not Hispanic or Latino
    		 92 92
        Unknown or Not Reported
    		 9 9
    Race
    Units: Subjects
        American Indian or Alaska Native
    		 0 0
        Asian
    		 49 49
        Native Hawaiian or Other Pacific Islander
    		 0 0
        White
    		 44 44
        More than one race
    		 0 0
        Unknown or Not Reported
    		 9 9
        Black or African American
    		 1 1
    Height
    Units: centimetres (cm)
        arithmetic mean (standard deviation)
    		 165.86 ( 10.172 ) -
    Weight
    Units: kilograms (kg)
        arithmetic mean (standard deviation)
    		 69.23 ( 15.409 ) -

    End points

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    End points reporting groups
    Reporting group title
    Brigatinib 90 mg/180mg With Optional Dose Escalation to 240 mg
    Reporting group description
    		 Participants received brigatinib 90 mg, tablets, orally, once daily (QD) for 7 days, followed by brigatinib 180 mg, tablets, orally, QD for until objective disease progression per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, as assessed by the investigator, or intolerable toxicity. Participants who experienced progression on the 180 mg dose and had not experienced toxicities greater than Grade 2 had the option to receive brigatinib 240 mg QD based on investigator’s discretion, up to 28 months from start of enrollment until data cut-off: 20 May 2021.

    Subject analysis set title
    Brigatinib 90/180 mg
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Brigatinib 90 mg, tablets, orally, QD for 7 days, followed by Brigatinib 180 mg, tablets, orally, QD for until objective disease progression per RECIST version 1.1, as assessed by the investigator, or intolerable toxicity up to approximately 28 months from start of enrollment till data cut-off: 20 May 2021. Participants who experienced progression on any doses but judged as still benefiting from the study treatment by the investigator continued to use the current dose, up to study end.

    Subject analysis set title
    Brigatinib 240 mg
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants who experienced progression on the 180 mg dose and had not experienced toxicities greater than Grade 2 had the option to receive brigatinib 240 mg QD from start of enrollment based on investigator’s discretion up to data-cut off: 20 May 2021 (approximately 28 months). Participants who experienced progression on any doses but judged as still benefiting from the study treatment by the investigator continued to use the current dose, up to study end.

    Primary: Confirmed Objective Response Rate (ORR) Using RECIST v1.1 as Assessed by the Independent Review Committee (IRC)

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    End point title
    		 Confirmed Objective Response Rate (ORR) Using RECIST v1.1 as Assessed by the Independent Review Committee (IRC) [1]
    End point description
    Confirmed ORR is defined as the percentage of the participants who are confirmed to have achieved complete response (CR) or partial response (PR), per RECIST version 1.1 (confirmed ≥4 weeks after initial response), after the initiation of study treatment. CR: disappearance of all extranodal target lesions and all pathological lymph nodes must have decreased to <10 mm in short axis and PR: at least a 30% decrease in the sum of the longest diameters (SLD) of target lesions taking as reference the Baseline sum diameters. Percentages were rounded off to the nearest single decimal place. Full Analysis Population included all participants who received at least 1 dose of brigatinib.
    End point type
    Primary
    End point timeframe
    Up to approximately 20 months from the start of enrollment till data cut-off 30 September 2020
    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: Single arm statistical analysis was performed but is not reported here to prevent an error. The p-value was 0.0763 and was based on the comparison of the confirm ORR among the 90/180mg group against a fixed response rate of 20%. The calculation was based on an exact binomial test with a total 1-sided alpha level of 0.025 at primary analysis.
    End point values
    		 Brigatinib 90 mg/180mg With Optional Dose Escalation to 240 mg
    Number of subjects analysed
    103
    Units: percentage of participants
        number (confidence interval 95%)
    26.2 (18.0 to 35.8)
    No statistical analyses for this end point

    Secondary: Confirmed ORR Using RECIST v1.1 as Assessed by the Investigator

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    End point title
    		 Confirmed ORR Using RECIST v1.1 as Assessed by the Investigator
    End point description
    Confirmed ORR is defined as the percentage of the participants who are confirmed to have achieved CR or PR, per RECIST version 1.1 (confirmed ≥4 weeks after initial response), after the initiation of study treatment. CR: disappearance of all extranodal target lesions and all pathological lymph nodes must have decreased to <10 mm in short axis and PR: at least a 30% decrease in the SLD of target lesions taking as reference the baseline sum diameters. Percentages were rounded off to the nearest single decimal place. Full Analysis Population included all participants who received at least 1 dose of brigatinib.
    End point type
    Secondary
    End point timeframe
    Up to approximately 28 months
    End point values
    		 Brigatinib 90 mg/180mg With Optional Dose Escalation to 240 mg
    Number of subjects analysed
    103
    Units: percentage of participants
        number (confidence interval 95%)
    26.2 (18.0 to 35.8)
    No statistical analyses for this end point

    Secondary: Duration of Response (DOR) as Assessed by the IRC and the Investigator

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    End point title
    		 Duration of Response (DOR) as Assessed by the IRC and the Investigator
    End point description
    DOR is defined as the time interval from the time that the measurement criteria are first met for CR or PR until the first date that the progressive disease (PD) is objectively documented, or death. CR: disappearance of all extranodal target lesions and all pathological lymph nodes must have decreased to <10 mm in short axis. PR: at least a 30% decrease in the SLD of target lesions taking as reference the Baseline sum diameters. PD: SLD increased by at least 20% from the smallest value on study (including Baseline, if that is the smallest). SLD must also demonstrate an absolute increase of at least 5 mm (2 lesions increasing from, for example, 2 mm to 3 mm, does not qualify). Full Analysis Population included all participants who received at least 1 dose of brigatinib. Subjects analysed: number of participants who were responders. '999' indicates: upper limit of 95 % confidence interval was not estimable due to insufficient number of events observed among responding participants.
    End point type
    Secondary
    End point timeframe
    Up to approximately 28 months
    End point values
    		 Brigatinib 90 mg/180mg With Optional Dose Escalation to 240 mg
    Number of subjects analysed
    27
    Units: months
    number (confidence interval 95%)
        IRC-Assessed DOR
    6.341 (5.552 to 999)
        Investigator-Assessed DOR
    6.735 (4.435 to 9.232)
    No statistical analyses for this end point

    Secondary: Progression-Free Survival (PFS) as Assessed by the IRC and the Investigator

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    End point title
    		 Progression-Free Survival (PFS) as Assessed by the IRC and the Investigator
    End point description
    PFS is 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. PFS was censored for participants without documented disease progression or death. Full Analysis Population included all participants who received at least 1 dose of brigatinib.
    End point type
    Secondary
    End point timeframe
    Up to approximately 28 Months
    End point values
    		 Brigatinib 90 mg/180mg With Optional Dose Escalation to 240 mg
    Number of subjects analysed
    103
    Units: months
    number (confidence interval 95%)
        IRC-Assessed PFS
    3.811 (3.515 to 5.848)
        Investigator-Assessed PFS
    3.811 (3.154 to 5.552)
    No statistical analyses for this end point

    Secondary: Disease Control Rate (DCR) as Assessed by the IRC and the Investigator

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    End point title
    		 Disease Control Rate (DCR) as Assessed by the IRC and the Investigator
    End point description
    DCR is defined as the percentage of participants who have achieved CR, PR or stable disease (SD) (in the case of SD, measurements must have met the SD criteria at least once after study entry at a minimum interval of 6 weeks) after the initiation of study treatment. CR: disappearance of all extranodal target lesions and all pathological lymph nodes must have decreased to <10 mm in short axis. 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 PD. Percentages were rounded off to the nearest single decimal place. Full Analysis Population included all participants who received at least 1 dose of brigatinib.
    End point type
    Secondary
    End point timeframe
    Up to approximately 28 months
    End point values
    		 Brigatinib 90 mg/180mg With Optional Dose Escalation to 240 mg
    Number of subjects analysed
    103
    Units: percentage of participants
    number (confidence interval 95%)
        IRC-Assessed DCR
    54.4 (44.3 to 64.2)
        Investigator-Assessed DCR
    59.2 (49.1 to 68.8)
    No statistical analyses for this end point

    Secondary: Time to Response as Assessed by the IRC and the Investigator

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    End point title
    		 Time to Response as Assessed by the IRC and the Investigator
    End point description
    Time to response is defined as the time interval from the date of the first dose of the study treatment until the initial observation of CR or PR. CR: disappearance of all extranodal target lesions and all pathological lymph nodes must have decreased to <10 mm in short axis. PR: at least a 30% decrease in the SLD of target lesions taking as reference the baseline sum diameters. Full Analysis Population included all participants who received at least 1 dose of brigatinib. Subjects analysed is the number of participants who were responders.
    End point type
    Secondary
    End point timeframe
    Up to approximately 28 months
    End point values
    		 Brigatinib 90 mg/180mg With Optional Dose Escalation to 240 mg
    Number of subjects analysed
    27
    Units: months
    number (confidence interval 95%)
        IRC-Assessed Time to Response
    1.807 (1.45 to 5.36)
        Investigator-Assessed Time to Response
    1.807 (1.58 to 10.87)
    No statistical analyses for this end point

    Secondary: Confirmed Intracranial Objective Response Rate (iORR) in Participants With Brain Metastases at Baseline, as Assessed by the IRC

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    End point title
    		 Confirmed Intracranial Objective Response Rate (iORR) in Participants With Brain Metastases at Baseline, as Assessed by the IRC
    End point description
    Confirmed iORR is defined as the proportion of the participants who have achieved CR or PR in the brain per a modification of RECIST version 1.1, after the initiation of study treatment, in participants with intracranial brain metastases at baseline. CR: disappearance of all extranodal target lesions and all pathological lymph nodes must have decreased to <10 mm in short axis. or partial response or PR: at least a 30% decrease in the SLD of target lesions taking as reference the baseline sum diameters. Percentages were rounded off to the nearest single decimal place. Intracranial central nervous system (iCNS) disease population included those participants in the Full Analysis Population who were determined by the IRC to have iCNS metastases at baseline, regardless of whether they had at least 1 lesion that qualified as a target lesion in their baseline assessment by the IRC.
    End point type
    Secondary
    End point timeframe
    Up to approximately 28 months
    End point values
    		 Brigatinib 90 mg/180mg With Optional Dose Escalation to 240 mg
    Number of subjects analysed
    55
    Units: percentage of participants
        number (confidence interval 95%)
    14.5 (6.5 to 26.7)
    No statistical analyses for this end point

    Secondary: Duration of Intracranial Response in Participants With Brain Metastases at Baseline, as Assessed by the IRC

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    End point title
    		 Duration of Intracranial Response in Participants With Brain Metastases at Baseline, as Assessed by the IRC
    End point description
    Duration of intracranial response:time interval from time that measurement criteria are first met for CR/PR until first date that PD (including baseline, if that is smallest). SLD must also demonstrate an absolute increase of at least 5mm.(2 lesions increasing from, for example,2mm-3mm,does not qualify)in brain is objectively documented/death,in participants with intracranial metastases at baseline.CR:disappearance of all extranodal target lesions&all pathological lymph nodes must have decreased to<10 mm in short axis/partial response/PR: at least a 30% decrease in SLD of target lesions taking as reference baseline sum diameters in brain.PD:SLD increased by at least 20% from smallest value on study. Analysis population: iCNS disease population. Subjects analyed: subjects who were responders. '9999' indicates the median and upper limit of 95 % confidence interval was not estimable due to insufficient number of events observed among the responding participants.
    End point type
    Secondary
    End point timeframe
    Up to approximately 28 months
    End point values
    		 Brigatinib 90 mg/180mg With Optional Dose Escalation to 240 mg
    Number of subjects analysed
    8
    Units: months
        median (confidence interval 95%)
    9999 (5.717 to 9999)
    No statistical analyses for this end point

    Secondary: Intracranial Progression-Free Survival (iPFS) in Participants With Brain Metastases at Baseline, as Assessed by the IRC

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    End point title
    		 Intracranial Progression-Free Survival (iPFS) in Participants With Brain Metastases at Baseline, as Assessed by the IRC
    End point description
    iPFS is defined as the time interval from the date of the first dose of the study treatment until the first date at which intracranial brain disease progression is objectively documented, or death due to any cause, whichever occurs first, in participants with intracranial metastases at enrollment. iPFS were censored for participants without documented intracranial disease progression or death. iCNS disease population included of those participants in the Full Analysis Population who were determined by the IRC to have iCNS metastases at baseline, regardless of whether they had at least 1 lesion that qualified as a target lesion in their Baseline assessment by the IRC.
    End point type
    Secondary
    End point timeframe
    Up to approximately 28 months
    End point values
    		 Brigatinib 90 mg/180mg With Optional Dose Escalation to 240 mg
    Number of subjects analysed
    55
    Units: months
        median (confidence interval 95%)
    5.224 (3.515 to 7.392)
    No statistical analyses for this end point

    Secondary: Overall Survival (OS)

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    End point title
    		 Overall Survival (OS)
    End point 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. It was censored on the date of last contact for those participants who were alive. Full Analysis Population included all participants who received at least 1 dose of brigatinib. '99999' indicates that the upper limit of 95 % confidence interval was not estimable due to insufficient number of events observed among the responding participants.
    End point type
    Secondary
    End point timeframe
    Up to approximately 28 months
    End point values
    		 Brigatinib 90 mg/180mg With Optional Dose Escalation to 240 mg
    Number of subjects analysed
    103
    Units: months
        median (confidence interval 95%)
    21.290 (12.189 to 99999)
    No statistical analyses for this end point

    Secondary: Number of Participants With One or More Treatment-emergent Adverse Event (TEAE)

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    End point title
    		 Number of Participants With One or More Treatment-emergent Adverse Event (TEAE)
    End point description
    AE means any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to the medicinal product. This includes any newly occurring event, or a previous condition that has increased in severity or frequency since the administration of study drug. TEAE: any AE either reported for the first time or worsening of a pre-existing event after first dose of study drug and within 30 days of the last administration of study drug. Safety Analysis Population included all participants who received at least 1 dose of brigatinib. As pre-specified in protocol, AEs are reported for 2 sets/arms. Arm 1 (brigatinib 90/180 mg) and Arm 2 (brigatinib 240 mg).
    End point type
    Secondary
    End point timeframe
    First dose of study drug up to 30 days after last dose (approximately 5 years)
    End point values
    		 Brigatinib 90/180 mg Brigatinib 240 mg
    Number of subjects analysed
    103
    13
    Units: participants
    103
    12
    No statistical analyses for this end point

    Secondary: Number of Participants With Improvement in Health-Related Quality of Life (HRQOL) Based on European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Score

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    End point title
    		 Number of Participants With Improvement in Health-Related Quality of Life (HRQOL) Based on European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Score
    End point description
    EORTC QLQ-C30 incorporates 5 functional scales(physical functioning,role functioning,emotional functioning,cognitive functioning,&social functioning),1 global health status scale, 3 symptom scales(fatigue, nausea&vomiting,& pain),&6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea,& financial difficulties). EORTC QLQ-C30 contains 28 questions (4-point scale where 1=Not at all [best] to 4=Very Much [worst]) &2 questions (7-point scale where 1=Very poor [worst] to 7= Excellent [best]). Raw scores are converted into scale scores ranging from 0 to 100. For functional scales&global health status scale, higher scores: better quality of life (QOL); for symptom scales, lower scores represent better QOL. Improvement:change from baseline of 10/more points higher for functional scales&10/more points lower for symptom scales.FAS.Subjects analysed:participants with data available for analysis.'n': number of participants with data available for analysis for specified category.
    End point type
    Secondary
    End point timeframe
    Up to approximately 28 months
    End point values
    		 Brigatinib 90 mg/180mg With Optional Dose Escalation to 240 mg
    Number of subjects analysed
    93
    Units: participants
        Global Health Status/QoL(n=93)
    52
        Physical Functioning (n=93)
    55
        Role Functioning (n=93)
    53
        Role Functioning Emotional Functioning(n=93)
    36
        Cognitive Functioning (n=93)
    47
        Social Functioning (n=93)
    53
        Fatigue (n=93)
    55
        Nausea and Vomiting(n=93)
    21
        Pain (n=93)
    48
        Dyspnoea Raw(n=93)
    26
        Insomnia (n=93)
    40
        Appetite Loss (n=93)
    30
        Constipation (n=92)
    23
        Diarrhoea (n=93)
    27
        Financial Difficulties(n=93)
    27
    No statistical analyses for this end point

    Secondary: Number of Participants With Improvement of HRQOL Based on EORTC QLQ- Lung Cancer (LC) 13

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    End point title
    		 Number of Participants With Improvement of HRQOL Based on EORTC QLQ- Lung Cancer (LC) 13
    End point description
    HRQOL scores was assessed with EORTC, its lung cancer module QLQ-LC13. QLQ-LC13 contains 13 questions assessing lung cancer-associated symptoms (cough, hemoptysis, dyspnea, and site-specific pain), treatment-related side effects (sore mouth, dysphagia, peripheral neuropathy, and alopecia), and use of pain medication. Scale score range: 0 to 100. Higher symptom score = greater degree of symptom severity. Improvement is defined as a change from baseline of 10 or more points lower for symptom scales. Full Analysis Population included all participants who received at least 1 dose of brigatinib. Subjects analysed is the number of participants with data available for analysis. 'n' indicates the number of participants with data available for analysis for the specified category.
    End point type
    Secondary
    End point timeframe
    Up to approximately 28 months
    End point values
    		 Brigatinib 90 mg/180mg With Optional Dose Escalation to 240 mg
    Number of subjects analysed
    93
    Units: participants
        Composite Endpoint Score (n=93)
    61
        Dyspnoea (n=93)
    45
        Coughing (n=93)
    37
        Haemoptysis (n=93)
    4
        Sore Mouth (n=93)
    6
        Dysphagia (n=93)
    4
        Peripheral Neuropathy (n=93)
    25
        Alopecia (n=93)
    14
        Pain in Chest (n=93)
    24
        Pain in Arm or Shoulder (n=93)
    23
        Pain in Other Parts (n=92)
    41
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    First dose of study drug up to 30 days after last dose (approximately 5 years)
    Adverse event reporting additional description
    Safety Analysis Population: participants who received at least 1 dose of brigatinib. As pre-specified in protocol, AEs are reported for 2 sets/arms. Arm 1 (brigatinib 90/180 mg) and Arm 2 (brigatinib 240 mg).
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    23.0
    Reporting groups
    Reporting group title
    Brigatinib 240 mg
    Reporting group description
    		 Participants who experienced progression on the 180 mg dose and had not experienced toxicities greater than Grade 2 had the option to receive brigatinib 240 mg QD from start of enrolment based on investigator’s discretion up to data-cut off: 30 September 2020 (approximately 20 months). Participants who experienced progression on any doses but judged as still benefiting from the study treatment by the investigator may continue to use the current dose, up to study end.

    Reporting group title
    Brigatinib 90/180 mg
    Reporting group description
    		 Participants received brigatinib 90 mg, tablets, orally, QD for 7 days, followed by brigatinib 180 mg, tablets, orally, QD for until objective disease progression per RECIST version 1.1, as assessed by the investigator, or intolerable toxicity. Participants who experienced progression on the 180 mg dose and had not experienced toxicities greater than Grade 2 had the option to receive brigatinib 240 mg QD based on investigator’s discretion, up to 28 months from start of enrollment until data cut-off: 20 May 2021. 1 Participant who experienced progression on any doses but judged as still benefiting from the study treatment by the investigator continued to receive brigatinib 180 mg, tablets, orally, once daily up to study end.

    Serious adverse events
    		 Brigatinib 240 mg Brigatinib 90/180 mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    3 / 13 (23.08%)
    48 / 103 (46.60%)
         number of deaths (all causes)
    5
    44
         number of deaths resulting from adverse events
    0
    17
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Cancer pain
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung neoplasm malignant
         subjects affected / exposed
    0 / 13 (0.00%)
    2 / 103 (1.94%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastases to biliary tract
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastases to central nervous system
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Metastases to meninges
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Neoplasm progression
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Non-small cell lung cancer
         subjects affected / exposed
    0 / 13 (0.00%)
    2 / 103 (1.94%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    Tumour associated fever
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Hypovolaemic shock
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    0 / 13 (0.00%)
    2 / 103 (1.94%)
         occurrences causally related to treatment / all
    0 / 0
    3 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Surgical and medical procedures
    Hospitalisation
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    0 / 13 (0.00%)
    2 / 103 (1.94%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pain
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral swelling
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Fatigue
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Disease progression
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Death
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Complication of device insertion
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Respiratory, thoracic and mediastinal disorders
    Bronchial haemorrhage
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    0 / 13 (0.00%)
    4 / 103 (3.88%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 3
    Malignant pleural effusion
         subjects affected / exposed
    0 / 13 (0.00%)
    2 / 103 (1.94%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    0 / 13 (0.00%)
    2 / 103 (1.94%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary artery thrombosis
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary oedema
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Pulmonary embolism
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Liver function test abnormal
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Craniofacial fracture
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Cardiac failure
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Atrial flutter
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Spinal cord compression
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral haemorrhage
         subjects affected / exposed
    0 / 13 (0.00%)
    2 / 103 (1.94%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Epilepsy
         subjects affected / exposed
    0 / 13 (0.00%)
    2 / 103 (1.94%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Moyamoya disease
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Paraesthesia
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 103 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sciatica
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    0 / 13 (0.00%)
    3 / 103 (2.91%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Neutropenia
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Duodenal obstruction
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Dysuria
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 103 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Intervertebral disc protrusion
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Back pain
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arthralgia
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Appendicitis
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal sepsis
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Sepsis
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 13 (0.00%)
    5 / 103 (4.85%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Meningitis
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infectious pleural effusion
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hyperkalaemia
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypercalcaemia
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gout
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 103 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Decreased appetite
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 103 (0.97%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Brigatinib 240 mg Brigatinib 90/180 mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    12 / 13 (92.31%)
    98 / 103 (95.15%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    3 / 13 (23.08%)
    20 / 103 (19.42%)
         occurrences all number
    4
    32
    General disorders and administration site conditions
    Swelling face
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 103 (0.00%)
         occurrences all number
    1
    0
    Oedema peripheral
         subjects affected / exposed
    1 / 13 (7.69%)
    8 / 103 (7.77%)
         occurrences all number
    1
    9
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 13 (0.00%)
    8 / 103 (7.77%)
         occurrences all number
    0
    9
    Fatigue
         subjects affected / exposed
    1 / 13 (7.69%)
    4 / 103 (3.88%)
         occurrences all number
    1
    4
    Chest pain
         subjects affected / exposed
    1 / 13 (7.69%)
    4 / 103 (3.88%)
         occurrences all number
    1
    4
    Asthenia
         subjects affected / exposed
    3 / 13 (23.08%)
    13 / 103 (12.62%)
         occurrences all number
    5
    15
    Pyrexia
         subjects affected / exposed
    2 / 13 (15.38%)
    13 / 103 (12.62%)
         occurrences all number
    2
    15
    Mucosal inflammation
         subjects affected / exposed
    2 / 13 (15.38%)
    2 / 103 (1.94%)
         occurrences all number
    3
    2
    Immune system disorders
    Cytokine release syndrome
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 103 (0.00%)
         occurrences all number
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    3 / 13 (23.08%)
    25 / 103 (24.27%)
         occurrences all number
    3
    30
    Epistaxis
         subjects affected / exposed
    1 / 13 (7.69%)
    3 / 103 (2.91%)
         occurrences all number
    1
    5
    Dyspnoea
         subjects affected / exposed
    1 / 13 (7.69%)
    12 / 103 (11.65%)
         occurrences all number
    1
    16
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    1 / 13 (7.69%)
    6 / 103 (5.83%)
         occurrences all number
    1
    6
    Insomnia
         subjects affected / exposed
    1 / 13 (7.69%)
    3 / 103 (2.91%)
         occurrences all number
    1
    3
    Persistent depressive disorder
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 103 (0.00%)
         occurrences all number
    1
    0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    2 / 13 (15.38%)
    19 / 103 (18.45%)
         occurrences all number
    2
    31
    Amylase increased
         subjects affected / exposed
    2 / 13 (15.38%)
    16 / 103 (15.53%)
         occurrences all number
    2
    35
    Aspartate aminotransferase increased
         subjects affected / exposed
    3 / 13 (23.08%)
    22 / 103 (21.36%)
         occurrences all number
    4
    35
    Blood alkaline phosphatase increased
         subjects affected / exposed
    0 / 13 (0.00%)
    9 / 103 (8.74%)
         occurrences all number
    0
    14
    Blood bilirubin increased
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 103 (0.00%)
         occurrences all number
    1
    0
    Blood calcium increased
         subjects affected / exposed
    1 / 13 (7.69%)
    2 / 103 (1.94%)
         occurrences all number
    1
    2
    Blood cholesterol increased
         subjects affected / exposed
    2 / 13 (15.38%)
    5 / 103 (4.85%)
         occurrences all number
    2
    7
    Blood creatine phosphokinase increased
         subjects affected / exposed
    5 / 13 (38.46%)
    35 / 103 (33.98%)
         occurrences all number
    7
    87
    Blood creatinine increased
         subjects affected / exposed
    1 / 13 (7.69%)
    5 / 103 (4.85%)
         occurrences all number
    1
    8
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    0 / 13 (0.00%)
    8 / 103 (7.77%)
         occurrences all number
    0
    12
    Lipase increased
         subjects affected / exposed
    1 / 13 (7.69%)
    19 / 103 (18.45%)
         occurrences all number
    2
    29
    Platelet count decreased
         subjects affected / exposed
    1 / 13 (7.69%)
    3 / 103 (2.91%)
         occurrences all number
    1
    3
    Weight decreased
         subjects affected / exposed
    0 / 13 (0.00%)
    14 / 103 (13.59%)
         occurrences all number
    0
    16
    Congenital, familial and genetic disorders
    Hypertrophic cardiomyopathy
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 103 (0.00%)
         occurrences all number
    1
    0
    Cardiac disorders
    Ventricular extrasystoles
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 103 (0.00%)
         occurrences all number
    1
    0
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    0 / 13 (0.00%)
    10 / 103 (9.71%)
         occurrences all number
    0
    13
    Dysgeusia
         subjects affected / exposed
    1 / 13 (7.69%)
    2 / 103 (1.94%)
         occurrences all number
    1
    2
    Headache
         subjects affected / exposed
    2 / 13 (15.38%)
    16 / 103 (15.53%)
         occurrences all number
    3
    16
    Paraesthesia
         subjects affected / exposed
    1 / 13 (7.69%)
    4 / 103 (3.88%)
         occurrences all number
    1
    5
    Tunnel vision
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 103 (0.00%)
         occurrences all number
    2
    0
    Blood and lymphatic system disorders
    Neutropenia
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 103 (0.97%)
         occurrences all number
    1
    1
    Lymphopenia
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 103 (0.00%)
         occurrences all number
    1
    0
    Anaemia
         subjects affected / exposed
    1 / 13 (7.69%)
    10 / 103 (9.71%)
         occurrences all number
    1
    16
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    7 / 13 (53.85%)
    41 / 103 (39.81%)
         occurrences all number
    7
    60
    Anal haemorrhage
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 103 (0.00%)
         occurrences all number
    2
    0
    Abdominal pain upper
         subjects affected / exposed
    0 / 13 (0.00%)
    6 / 103 (5.83%)
         occurrences all number
    0
    7
    Constipation
         subjects affected / exposed
    1 / 13 (7.69%)
    11 / 103 (10.68%)
         occurrences all number
    1
    13
    Vomiting
         subjects affected / exposed
    2 / 13 (15.38%)
    18 / 103 (17.48%)
         occurrences all number
    2
    25
    Nausea
         subjects affected / exposed
    2 / 13 (15.38%)
    29 / 103 (28.16%)
         occurrences all number
    2
    44
    Skin and subcutaneous tissue disorders
    Pruritus
         subjects affected / exposed
    1 / 13 (7.69%)
    5 / 103 (4.85%)
         occurrences all number
    2
    5
    Rash
         subjects affected / exposed
    2 / 13 (15.38%)
    8 / 103 (7.77%)
         occurrences all number
    2
    19
    Rash pruritic
         subjects affected / exposed
    1 / 13 (7.69%)
    2 / 103 (1.94%)
         occurrences all number
    1
    2
    Skin exfoliation
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 103 (0.00%)
         occurrences all number
    1
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1 / 13 (7.69%)
    7 / 103 (6.80%)
         occurrences all number
    1
    8
    Back pain
         subjects affected / exposed
    0 / 13 (0.00%)
    12 / 103 (11.65%)
         occurrences all number
    0
    13
    Bone pain
         subjects affected / exposed
    1 / 13 (7.69%)
    2 / 103 (1.94%)
         occurrences all number
    1
    2
    Musculoskeletal chest pain
         subjects affected / exposed
    0 / 13 (0.00%)
    6 / 103 (5.83%)
         occurrences all number
    0
    6
    Myalgia
         subjects affected / exposed
    1 / 13 (7.69%)
    7 / 103 (6.80%)
         occurrences all number
    1
    11
    Pain in extremity
         subjects affected / exposed
    0 / 13 (0.00%)
    13 / 103 (12.62%)
         occurrences all number
    0
    14
    Infections and infestations
    Localised infection
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 103 (0.00%)
         occurrences all number
    1
    0
    Pneumonia
         subjects affected / exposed
    0 / 13 (0.00%)
    8 / 103 (7.77%)
         occurrences all number
    0
    9
    Tonsillitis
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 103 (0.00%)
         occurrences all number
    1
    0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    1 / 13 (7.69%)
    11 / 103 (10.68%)
         occurrences all number
    2
    12
    Hyperglycaemia
         subjects affected / exposed
    1 / 13 (7.69%)
    9 / 103 (8.74%)
         occurrences all number
    2
    14
    Hypertriglyceridaemia
         subjects affected / exposed
    1 / 13 (7.69%)
    3 / 103 (2.91%)
         occurrences all number
    1
    3
    Hypoalbuminaemia
         subjects affected / exposed
    1 / 13 (7.69%)
    3 / 103 (2.91%)
         occurrences all number
    1
    3
    Hypokalaemia
         subjects affected / exposed
    0 / 13 (0.00%)
    7 / 103 (6.80%)
         occurrences all number
    0
    7
    Hyponatraemia
         subjects affected / exposed
    0 / 13 (0.00%)
    7 / 103 (6.80%)
         occurrences all number
    0
    11
    Hypophosphataemia
         subjects affected / exposed
    1 / 13 (7.69%)
    2 / 103 (1.94%)
         occurrences all number
    2
    2

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    10 Apr 2019
    The following changes were as per amendment 02: 1. Updated primary objective of the study. 2. Corrected timing of AE assessments. 3. Revised Study Design. 4. Revised minimum age-related inclusion criterion.
    27 Sep 2019
    The primary reason for amendment 03 was to remove the interim analysis.
    24 Sep 2020
    The primary reason for amendment 04 was to maintain patient safety, confidentiality, and study integrity in the context of healthcare challenges presented by the coronavirus disease 2019 (COVID-19) public health emergency.
    12 Feb 2021
    The following changes were as per amendment 05: 1. Modified definition of end of study to include termination of study by sponsor. 2. Section added to provide posttrial access to brigatinib.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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