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| ID | Type | Description | Link |
|---|---|---|---|
| 2013-002134-21 | EudraCT Number | ||
| U1111-1196-8246 | Other Identifier | WHO |
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The purpose of this study is to evaluate the efficacy and safety of two different dosing regimens of brigatinib (AP26113) in participants with ALK-positive locally advanced or metastatic non-small cell lung cancer (NSCLC) whose disease has progressed on therapy with crizotinib.
The drug being tested in this study is called brigatinib (AP26113). Brigatinib was tested to treat people with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) who have progressed on or were intolerant to crizotinib. This study looked at the efficacy of brigatinib.
The study enrolled 222 patients. Participants were randomly assigned (by chance, like flipping a coin) to one of the two treatment groups:
All participants were asked to take a tablet, orally once daily until disease progression or intolerable toxicity. Participants in Brigatinib 90 mg - 180 mg received 180 mg with a 7-day lead-in at 90 mg.
This multi-center trial was conducted worldwide. The overall time to participate in this study is up to 3 years. Participants will make multiple visits to the clinic, and 3 months after the End-of-Treatment visit. Follow-up is intended to continue for 2 years after the last participants was enrolled into the study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Brigatinib 90 mg | Experimental | 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). |
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| Brigatinib 90 mg - 180 mg | Experimental | 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). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Brigatinib | Drug | Brigatinib tablets |
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| Measure | Description | Time Frame |
|---|---|---|
| Confirmed Objective Response Rate (ORR) as Assessed by Investigator | 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%. | 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) |
| Measure | Description | Time Frame |
|---|---|---|
| Confirmed Objective Response Rate (ORR) as Assessed by Independent Review Committee (IRC) | 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. |
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Inclusion Criteria:
Have histologically or cytologically confirmed locally advanced or metastatic Non-small Cell Lung Cancer (NSCLC) that is anaplastic lymphoma kinase (ALK+).
Must meet one of the following two criteria:
Had progressive disease while on crizotinib, as assessed by the investigator or treating physician.
Have at least 1 measurable lesion per RECIST v1.1. Note: Previously irradiated lesions may not be used for target lesions, unless there is unambiguous radiological progression after radiotherapy. Brain lesions may not be used as target lesions if they were: 1) previously treated with whole brain radiation therapy (WBRT) within 3 months, or 2) previously treated by stereotactic radiosurgery (SRS) or surgical resection.
Recovered from toxicities related to prior anticancer therapy to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, v4.0) grade ≤2.
Are a male or female participants ≥18 years old.
Have a life expectancy ≥3 months.
Have adequate organ and hematologic function, as determined by:
Have Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
Have normal QT interval on screening electrocardiogram (ECG) evaluation, defined as QT interval corrected (Fridericia) (QTcF) of ≤450 ms in males or ≤470 ms in females.
For female participants of childbearing potential, a negative pregnancy test must be documented prior to enrollment.
Female and male participants who are fertile must agree to use a highly effective form of contraception with their sexual partners throughout study participation.
Must provide a signed and dated informed consent indicating that the participants has been informed of all pertinent aspects of the study, including the potential risks, and is willingly participating.
Have the willingness and ability to comply with scheduled visits and study procedures.
Exclusion Criteria:
Received any prior ALK-targeted TKI other than crizotinib.
Received crizotinib within 3 days of the first dose of brigatinib (Day 1, Cycle 1).
Received cytotoxic chemotherapy, investigational agents, or radiation within 14 days, except SRS or stereotactic body radiosurgery.
Received monoclonal antibodies or had major surgery within 30 days of the first dose of brigatinib (Day 1, Cycle 1).
Have been diagnosed with another primary malignancy within the past 3 years (except for adequately treated non-melanoma skin cancer, cervical cancer in situ, or prostate cancer, which are allowed within 3 years).
Have symptomatic CNS metastases that are neurologically unstable or require an increasing dose of corticosteroids.
Have current spinal cord compression.
Have significant, uncontrolled, or active cardiovascular disease, specifically including, but not restricted to:
Have a history or the presence of pulmonary interstitial disease or drug-related pneumonitis.
Have an ongoing or active infection. The requirement for intravenous (IV) antibiotics is considered active infection.
Have a known history of human immunodeficiency virus (HIV). Testing is not required in the absence of history.
Have a history of or active significant gastrointestinal (GI) bleeding within 3 months of the first dose of brigatinib.
Have a known or suspected hypersensitivity to brigatinib or its excipients.
Have malabsorption syndrome or other GI illness that could affect oral absorption of the study drug.
Have any condition or illness that, in the opinion of the investigator, would compromise participants safety or interfere with evaluation of the drug study.
Be pregnant or breastfeeding.
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director Clinical Science | Takeda | Study Director |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31125274 | Derived | Kawata AK, Lenderking WR, Eseyin OR, Kerstein D, Huang J, Huang H, Zhang P, Lin HM. Converting EORTC QLQ-C30 scores to utility scores in the brigatinib ALTA study. J Med Econ. 2019 Sep;22(9):924-935. doi: 10.1080/13696998.2019.1624080. Epub 2019 Jun 25. | |
| 29768119 | Derived | Camidge DR, Kim DW, Tiseo M, Langer CJ, Ahn MJ, Shaw AT, Huber RM, Hochmair MJ, Lee DH, Bazhenova LA, Gold KA, Ou SI, West HL, Reichmann W, Haney J, Clackson T, Kerstein D, Gettinger SN. Exploratory Analysis of Brigatinib Activity in Patients With Anaplastic Lymphoma Kinase-Positive Non-Small-Cell Lung Cancer and Brain Metastases in Two Clinical Trials. J Clin Oncol. 2018 Sep 10;36(26):2693-2701. doi: 10.1200/JCO.2017.77.5841. Epub 2018 May 16. |
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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.
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | Brigatinib 90 mg | 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). |
| FG001 | Brigatinib 90 mg - 180 mg |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Aug 24, 2015 | Feb 18, 2021 |
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| 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) |
| Confirmed Intracranial Central Nervous System Objective Response Rate (CNS ORR) in Participants With Measurable Active Brain Metastases | 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. | 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 |
| Confirmed Intracranial Central Nervous System Objective Response Rate (CNS ORR) in Participants With Only Non-measurable Active Brain Metastases | 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. | 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 |
| Intracranial CNS Progression Free Survival (PFS) in Participants With Active Brain Metastases | 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. | 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 |
| Time to Response | 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. | Up to approximately 69 months |
| Duration of Response | 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. | Up to approximately 69 months |
| Time on Treatment | 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. | Up to approximately 69 months |
| Disease Control Rate (DCR) | 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. | 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) |
| Progression Free Survival (PFS) | 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. | Up to approximately 69 months |
| Overall Survival (OS) | 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. | Up to approximately 69 months |
| Number of Participants Who Had at Least One Treatment-Emergent Adverse Event (TEAE) | 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. | From first dose of study drug up to 30 days following the last dose of study drug (approximately up to 69 months) |
| Pre-dose Brigatinib Plasma Concentration | Day 1 Cycles 2, 3, 4 and 5 (each Cycle of 28-days) pre-dose |
| Patient-reported Symptoms Global Health Status/Quality of Life (QoL) Scores | 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. | Baseline and at each 28-day cycle up to end of the study (up to approximately 69 months) |
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).
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| COMPLETED | Completed = Participants who completed the treatment. |
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| NOT COMPLETED |
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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.
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| ID | Title | Description |
|---|---|---|
| BG000 | Brigatinib 90 mg | 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). |
| BG001 | Brigatinib 90 mg - 180 mg | 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). |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
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| Primary | Confirmed Objective Response Rate (ORR) as Assessed by Investigator | 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%. | ITT Population included all participants who were randomized to each regimen regardless of whether they received study drug or adhered to the assigned dose. | Posted | Number | 97.5% Confidence Interval | percentage of participants | 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) |
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| Secondary | Confirmed Objective Response Rate (ORR) as Assessed by Independent Review Committee (IRC) | 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. | ITT Population included all participants who were randomized to each regimen regardless of whether they received study drug or adhered to the assigned dose. | Posted | Number | 95% Confidence Interval | percentage of participants | 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) |
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| Secondary | Confirmed Intracranial Central Nervous System Objective Response Rate (CNS ORR) in Participants With Measurable Active Brain Metastases | 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. | 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. | Posted | Number | 95% Confidence Interval | percentage of participants | 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 |
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| Secondary | Confirmed Intracranial Central Nervous System Objective Response Rate (CNS ORR) in Participants With Only Non-measurable Active Brain Metastases | 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. | 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. | Posted | Number | 95% Confidence Interval | percentage of participants | 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 |
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| Secondary | Intracranial CNS Progression Free Survival (PFS) in Participants With Active Brain Metastases | 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. | 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. | Posted | Median | 95% Confidence Interval | months | 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 |
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| Secondary | Time to Response | 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. | 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. | Posted | Median | Full Range | months | Up to approximately 69 months |
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| Secondary | Duration of Response | 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. | 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. | Posted | Median | 95% Confidence Interval | months | Up to approximately 69 months |
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| Secondary | Time on Treatment | 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. | Safety Population included all participants who received at least one dose of study drug. | Posted | Median | Full Range | days | Up to approximately 69 months |
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| Secondary | Disease Control Rate (DCR) | 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. | ITT Population included all participants who were randomized to each regimen regardless of whether they received study drug or adhered to the assigned dose. | Posted | Number | 95% Confidence Interval | percentage of participants | 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) |
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| Secondary | Progression Free Survival (PFS) | 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. | ITT Population included all participants who were randomized to each regimen regardless of whether they received study drug or adhered to the assigned dose. | Posted | Median | 95% Confidence Interval | months | Up to approximately 69 months |
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| Secondary | Overall Survival (OS) | 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. | ITT Population included all participants who were randomized to each regimen regardless of whether they received study drug or adhered to the assigned dose. | Posted | Median | 95% Confidence Interval | months | Up to approximately 69 months |
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| Secondary | Number of Participants Who Had at Least One Treatment-Emergent Adverse Event (TEAE) | 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. | Safety Population included all participants who received at least one dose of study drug. | Posted | Number | participants | From first dose of study drug up to 30 days following the last dose of study drug (approximately up to 69 months) |
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| Secondary | Pre-dose Brigatinib Plasma Concentration | 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. | Posted | Mean | Standard Deviation | ng/ml | Day 1 Cycles 2, 3, 4 and 5 (each Cycle of 28-days) pre-dose |
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| Secondary | Patient-reported Symptoms Global Health Status/Quality of Life (QoL) Scores | 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. | 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. | Posted | Mean | Standard Deviation | unit on a scale | Baseline and at each 28-day cycle up to end of the study (up to approximately 69 months) |
|
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)
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.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Brigatinib 90 mg | 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). | 64 | 109 | 58 | 109 | 108 | 109 |
| EG001 | Brigatinib 90 mg - 180 mg | 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). | 54 | 110 | 69 | 110 | 105 | 110 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Neoplasm progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
| |
| Malignant pleural effusion | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
| |
| Metastases to central nervous system | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
| |
| Metastases to meninges | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
| |
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Appendicitis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Atypical pneumonia | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Meningitis bacterial | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Tuberculous pleurisy | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Urosepsis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Epilepsy | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Cerebrovascular accident | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Generalised tonic-clonic seizure | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Nervous system disorder | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Seizure | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Simple partial seizures | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Spinal cord compression | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Transient ischaemic attack | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Infusion site thrombosis | General disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Sudden death | General disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Head injury | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
| |
| Radiation necrosis | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
| |
| Radiation pneumonitis | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Food poisoning | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Small intestinal obstruction | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Pathological fracture | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Angioedema | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Dermatitis allergic | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Paraneoplastic dermatomyositis | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Rash erythematous | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Vertigo positional | Ear and labyrinth disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Cholangitis acute | Hepatobiliary disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Jaundice cholestatic | Hepatobiliary disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Hydronephrosis | Renal and urinary disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Renal impairment | Renal and urinary disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Macular oedema | Eye disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA 23.0 | Systematic Assessment |
| |
| Confusional state | Psychiatric disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Behcets syndrome | Vascular disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Squamous cell carcinoma of skin | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
| |
| Bowens disease | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
| |
| Metastases to peritoneum | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
| |
| Metastatic malignant melanoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
| |
| Thyroid cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
| |
| Tumour associated fever | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
| |
| Metastases to liver | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
| |
| Bronchopulmonary aspergillosis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Clostridium difficile colitis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Diverticulitis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Escherichia urinary tract infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Haematoma infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Peritonitis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Pyelonephritis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Skin infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Oesophagobronchial fistula | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Pneumonia aspiration | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Hemiparesis | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Aphasia | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Cognitive disorder | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Hyperaesthesia | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Intracranial pressure increased | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Tonic clonic movements | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Osteonecrosis | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Soft tissue necrosis | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Abdominal pain upper† | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Haematemesis | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Haematochezia | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Tooth socket haemorrhage | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
| |
| Hip fracture | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
| |
| Skin laceration | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Angina pectoris | Cardiac disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Supraventricular tachycardia | Cardiac disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Hepatic function abnormal† | Hepatobiliary disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Lymph node pain | Blood and lymphatic system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Iliac artery stenosis | Vascular disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA 23.0 | Systematic Assessment |
| |
| Device occlusion | Product Issues | MedDRA 23.0 | Systematic Assessment |
| |
| Euthanasia | General disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Non-cardiac chest pain | General disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 23.0 | Systematic Assessment |
| |
| General physical health deterioration | General disorders | MedDRA 23.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Memory impairment | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Blood creatine phosphokinase increased | Investigations | MedDRA 23.0 | Systematic Assessment |
| |
| Amylase increased | Investigations | MedDRA 23.0 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 23.0 | Systematic Assessment |
| |
| Lipase increased | Investigations | MedDRA 23.0 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 23.0 | Systematic Assessment |
| |
| Blood lactate dehydrogenase increased | Investigations | MedDRA 23.0 | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA 23.0 | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Dermatitis acneiform | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Vertigo | Ear and labyrinth disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Influenza like illness | General disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Non-cardiac chest pain | General disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Seizure | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Hypoaesthesia | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Cognitive disorder | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Tremor | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Blood alkaline phosphatase increased | Investigations | MedDRA 23.0 | Systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA 23.0 | Systematic Assessment |
| |
| Electrocardiogram QT prolonged | Investigations | MedDRA 23.0 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Herpes zoster | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Rash erythematous | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Rash pruritic | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Vision blurred | Eye disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
| |
| Palpitations | Cardiac disorders | MedDRA 23.0 | Systematic Assessment |
|
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Director | Takeda | +1-877-825-3327 | trialdisclosures@takeda.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Feb 25, 2016 | Feb 18, 2021 | SAP_001.pdf |
| ID | Term |
|---|---|
| D002289 | Carcinoma, Non-Small-Cell Lung |
| ID | Term |
|---|---|
| D002283 | Carcinoma, Bronchogenic |
| D001984 | Bronchial Neoplasms |
| D008175 | Lung Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C000598580 | brigatinib |
Not provided
Not provided
Not provided
| Male |
|
| Black or African American |
|
| Asian |
|
| Unknown |
|
| Not Hispanic or Latino |
|
| Austria |
|
| Belgium |
|
| Canada |
|
| Denmark |
|
| France |
|
| Germany |
|
| Hong Kong |
|
| Italy |
|
| Netherlands |
|
| Norway |
|
| Singapore |
|
| Spain |
|
| Sweden |
|
| Switzerland |
|
| United Kingdom |
|
| United States |
|
| Korea, Republic Of |
|
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).
|
|
| OG001 |
| Brigatinib 90 mg - 180 mg |
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). |
|
|
| OG001 |
| Brigatinib 90 mg - 180 mg |
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). |
|
|
|
|
|
|
|
|
|
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). |
|
|
|
|
|
| Counts |
|---|
| Participants |
|
|
|
| Brigatinib 90 mg - 180 mg |
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). |
|
|