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| ID | Type | Description | Link |
|---|---|---|---|
| U1111-1210-4363 | Other Identifier | WHO | |
| 2015-003447-19 | EudraCT Number |
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The purpose of the study is to compare the efficacy of brigatinib to that of crizotinib in ALK+ locally advanced or metastatic non-small cell lung cancer (NSCLC) participants naive to ALK inhibitors, as evidenced by progression-free survival (PFS).
The purpose of this phase III, randomized, open-label, comparative, multicenter, international study is to compare the efficacy and safety of brigatinib to that of crizotinib in ALK+ locally advanced or metastatic NSCLC participants who have not previously been treated with an ALK inhibitor. Participants will be stratified by the presence of CNS metastases at baseline and prior chemotherapy used for locally advanced or metastatic disease. Participants will be randomized in a 1:1 ratio to receive either brigatinib, 90 mg orally once daily (QD) for 7 days, then a 180 mg orally QD, or crizotinib, 250 mg orally twice daily (BID). Participants will receive treatment until disease progression, intolerable toxicity, consent withdrawal, or death. Crossover from crizotinib to brigatinib is also permitted.
The total estimated duration of the study is at least 4.5 years, including 1.5 years to accrue participants, with at least 3 years for treatment and follow-up.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Randomized Phase: Brigatinib 90 mg QD/180 QD | Experimental | Brigatinib 90 mg, tablets, orally, QD for first 7 days followed by 180 mg, orally, QD, in each 28-day cycle until PD, intolerable toxicity, consent withdrawal, or death (The median duration of exposure was 34.86 months). |
|
| Randomized Phase: Crizotinib 250 mg BID | Active Comparator | Crizotinib 250 mg, tablets, BID in each 28-day cycle until disease progression, intolerable toxicity, consent withdrawal, or death (The median duration of exposure was 9.26 months). |
|
| Crossover Phase: Brigatinib 90 mg QD/180 mg QD | Experimental | Participants who experienced PD as assessed by the BIRC or received radiotherapy to the brain while on 'Crizotinib 250 mg BID' therapy in Randomized Phase were crossed over. Following 10-day washout period, crossover participants received brigatinib 90 mg, tablets, orally, QD for first 7 days followed by 180 mg, tablets, orally, QD in each 28-day cycle up to end of the study (The median duration of exposure was 17.25 months). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Brigatinib | Drug | Brigatinib tablets |
|
| Measure | Description | Time Frame |
|---|---|---|
| Progression-free Survival (PFS) | PFS as assessed by Blinded Independent Review Committee (BIRC), per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, was defined as the time interval from the date of randomization until the date of the first documented PD event. The data was censored for participants without a PFS event. | Up to end of study (Up to 56 months) |
| Measure | Description | Time Frame |
|---|---|---|
| Confirmed Objective Response Rate (ORR) | ORR was defined as percentage of participants who achieved Complete response (CR) or Partial responses (PR) using Response Evaluation Criteria in Solid Tumors (RECIST) version (v). 1.1 criteria. CR is defined as disappearance of all extranodal target and non-target lesions. All pathological lymph nodes must have decreased to less than (<) 10 mm in short axis for target lesions and all lymph nodes must be non-pathological in size (<10 mm short axis), normalization of tumor marker level for non-target lesions. PR is at least a 30% decrease in SLD of target lesions, taking as reference baseline sum diameters. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Takeda | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| USOR - Arizona Oncology Associates - Sedona | Sedona | Arizona | 86336 | United States | ||
| Kaiser Permanente Bellflower Medical Offices |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41410381 | Derived | Ahn MJ, Delmonte A, Ghosh S, Hochmair M, Yang TY, Yang JC, Han JY, Hansen KH, Wu Y, Wan Y, Lin HM, Kretz J, Hupf B, Kurec AM, Churchill EN, Fram RJ, Cabasag CJ, Goriya V, Zhao Y, Campelo MRG. Real-world treatment patterns and subsequent treatment effectiveness following frontline brigatinib in the ALTA-1L trial. Future Oncol. 2025 Dec;21(30):3935-3945. doi: 10.1080/14796694.2025.2592527. Epub 2025 Dec 18. | |
| 39707229 |
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Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
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IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
Participants with anaplastic lymphoma kinase and non-small-cell lung cancer (ALK+ NSCLC) who had not previously received an ALK-targeted tyrosine kinase inhibitor (TKI) were enrolled in 1:1 ratio to receive brigatinib 90 mg for 7 days followed by 180 mg or crizotinib 250 mg. Participants from crizotinib arm who experienced progressive disease (PD) or received radiotherapy to the brain in Randomized Phase were crossed over to receive brigatinib 90 mg/180 mg in the Crossover Phase.
Participants took part in the study at 92 investigative sites in Australia, Hong Kong, Singapore, South Korea, Taiwan, Austria, Denmark, France, Germany, Italy, Luxembourg, Netherlands, Norway, Spain, Sweden, Switzerland, United Kingdom, Canada, and the United States of America from 26 May 2016 to 29 January 2021.
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| ID | Title | Description |
|---|---|---|
| FG000 | Randomized Phase: Brigatinib 90 mg QD/180 QD | Brigatinib 90 mg, tablets, orally, once daily (QD) for first 7 days followed by 180 mg, orally, QD, in each 28-day cycle until disease progression (PD), intolerable toxicity, consent withdrawal, or death (The median duration of exposure was 34.86 months). |
| FG001 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Randomized Phase |
|
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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 | May 12, 2020 | Jul 27, 2021 |
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| Crizotinib | Drug | Crizotinib tablets |
|
|
| Baseline up to end of treatment (Up to 36 months) |
| Confirmed Intracranial ORR (iORR) | ORR was defined as percentage of participants who achieved CR or PR in the central nervous system (CNS) in randomized participants with intracranial CNS metastasis at baseline. CR is defined as disappearance of all extranodal target and non-target lesions. All pathological lymph nodes must have decreased to <10 mm in short axis for target lesions and all lymph nodes must be non-pathological in size (<10 mm short axis), normalization of tumor marker level for non-target lesions. PR is at least a 30% decrease in the SLD of target lesions, taking as reference the baseline sum diameters. | Baseline up to end of treatment (Up to 36 months) |
| Intracranial Progression Free Survival | Intracranial PFS as assessed by BIRC, is defined as the time from randomization until first CNS PD is documented, or death due to any cause. PD is SLD increased by at least 20% from the smallest value on study (including baseline, if that is the smallest), the SLD must also demonstrate an absolute increase of at least 5 mm, and unequivocal progression of existing non-target lesions. | Baseline up to end of study (Up to 56 months) |
| Overall Survival (OS) | Overall survival is defined as the time from randomization until death due to any cause. | Baseline up to end of study (Up to 56 months) |
| Duration of Response (DOR) | Duration of response as assessed by BIRC, is defined as the time interval from the date that the criteria are first met for CR/PR (whichever is first recorded) until the first date that progressive disease (PD) is objectively documented. CR is defined as disappearance of all extranodal target and non-target lesions. All pathological lymph nodes must have decreased to <10 mm in short axis for target lesions and all lymph nodes must be non-pathological in size (<10 mm short axis), normalization of tumor marker level for non-target lesions. PR is at least a 30 % decrease in the SLD of target lesions, taking as reference the baseline sum diameters. PD is SLD increased by at least 20% from the smallest value on study (including baseline, if that is the smallest), the SLD must also demonstrate an absolute increase of at least 5 mm, and for non-target lesions, unequivocal progression of existing non-target lesions. | Baseline up to end of study (Up to 56 months) |
| Time to Response (TTR) | Time to response as assessed by BIRC, assessment and is defined as the time interval from the date of randomization until the initial observation of CR or PR. CR is defined as disappearance of all extranodal target and non-target lesions. All pathological lymph nodes must have decreased to <10 mm in short axis for target lesions and all lymph nodes must be non-pathological in size (<10 mm short axis), normalization of tumor marker level for non-target lesions. PR is at least a 30% decrease in the SLD of target lesions, taking as reference the baseline sum diameters. | Baseline up to end of treatment (Up to 36 months) |
| Disease Control Rate (DCR) | Disease control as assessed by BIRC, defined as percentage of randomized participants who have achieved CR, PR, or stable disease (SD) after randomization. CR defined as disappearance of all extranodal target and non-target lesions. All pathological lymph nodes must have decreased to <10 mm in short axis for target lesions and all lymph nodes must be non-pathological in size (<10 mm short axis), normalization of tumor marker level for non-target lesions. PR: at least a 30% decrease in SLD of target lesions, taking as reference baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. PD: SLD increased by at least 20% from the smallest value on study, SLD must also demonstrate an absolute increase of at least 5 mm, and unequivocal progression of existing non-target lesions. | Baseline up to end of treatment (Up to 36 months) |
| Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) | An AE is any untoward medical occurrence in a participant. An AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product whether or not considered related to the medicinal product. Any worsening of a preexisting condition which is temporally associated with the use of the study drug (i.e., occurs after the first dose of study drug) is also an AE. TEAEs are defined as AEs starting/worsening on or after the first dose of study treatment and no later than the earliest of 30 days after the last dose of the treatment to which the participant was assigned, or the day before start of brigatinib therapy in crossover participant. | From first dose up to 30 days after last dose of study drug (Up to approximately 37 months) |
| Change From Baseline in Global Health Status/Quality of Life as Assessed by EORTC QLQ-C30 (Version 3.0) | HRQoL: perceived quality of participant's life, includes self-reported multidimensional measures of physical and mental health. Patient-reported symptoms (PROs) and HRQoL will be collected by administering the european organisation for research and treatment of cancer (EORTC) quality of life (QLQ)-C30 questionnaire. EORTC-QLQ-C30 contains 30 items across 5 functional scales (physical, role, cognitive, emotional, and social), 9 symptom scales (fatigue, nausea and vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and financial difficulties) and a global health status/QOL scale. The 30 items have 4 response levels (not at all, a little, quite a bit, and very much), with 2 questions relying on a 7-point numeric rating scale. Raw scores are converted into overall score ranging from 0 to 100, where lower scores indicate better QOL. A negative change from Baseline indicates improvement. | Baseline and Month 36 |
| Bellflower |
| California |
| 90706 |
| United States |
| University of Colorado Cancer Center | Aurora | Colorado | 80045 | United States |
| Rocky Mountain Cancer Centers - Boulder | Boulder | Colorado | 80303-1385 | United States |
| Sylvester Comprehensive Cancer Center | Deerfield Beach | Florida | 33442 | United States |
| Beth Israel Deaconess Medical Center | Boston | Massachusetts | 02215 | United States |
| West Michigan Cancer Center | Kalamazoo | Michigan | 49007 | United States |
| Minnesota Oncology | Coon Rapids | Minnesota | 55433 | United States |
| Montefiore Medical Center | The Bronx | New York | 10461 | United States |
| Oncology Hematology Care - Blue Ash | Cincinnati | Ohio | 45242-5665 | United States |
| Stephenson Cancer Center | Oklahoma City | Oklahoma | 73104 | United States |
| Virginia Cancer Specialists - Fairfax Office | Fairfax | Virginia | 22031 | United States |
| Saint George Hospital | Kogarah | New South Wales | 2217 | Australia |
| Royal North Shore Hospital | St Leonards | New South Wales | 2065 | Australia |
| Monash Medical Centre | Bentleigh East | Victoria | 3165 | Australia |
| Saint Vincent's Hospital Melbourne | Fitzroy | Victoria | 3065 | Australia |
| Universitatsklinium St. Polten | Sankt Pölten | Lower Austria | 3100 | Austria |
| Otto-Wagner-Spital Baumgartner Hohe | Vienna | 1140 | Austria |
| Princess Margaret Cancer Centre | Toronto | Ontario | M5G 2M9 | Canada |
| Odense University Hospital | Odense C | 5000 | Denmark |
| Hopital Albert Michallon | Grenoble | Auvergne-Rhône-Alpes | 38043 | France |
| Centre Leon Berard | Lyon | Auvergne-Rhône-Alpes | 69008 | France |
| Centre de Lutte Contre le Cancer Francois Baclesse | Caen | Basse-normandie | 14076 | France |
| Hopital Charles Nicolle | Rouen | Haute-normandie | 76041 | France |
| Centre Hospitalier Universitaire Hopital Nord | Marseille | Provence-Alpes-Côte d'Azur Region | 13915 | France |
| Centre Hospitalier Intercommunal de Creteil | Créteil | Île-de-France Region | 94010 | France |
| Hopital Tenon | Paris | Île-de-France Region | 75020 | France |
| Universitatsklinik Freiburg | Freiburg im Breisgau | Baden-Wurttemberg | 79106 | Germany |
| Thoraxklinik Heidelberg gGmbH | Heidelberg | Baden-Wurttemberg | 69126 | Germany |
| Pius Hospital Oldenburg | Oldenburg | Lower Saxony | 26121 | Germany |
| Kliniken der Stadt Koeln gGmbH - Krankenhaus Merheim | Cologne | North Rhine-Westphalia | 51109 | Germany |
| Evangelische Lungenklinik Berlin | Berlin | 13125 | Germany |
| Studiengesellschaft Haemato-Onkologie Hamburg Prof. Laack und Partner | Hamburg | 20251 | Germany |
| Tuen Mun Hospital | Tuenmen | New Territories | Hong Kong |
| Queen Mary Hospital | Hong Kong | Hong Kong |
| Queen Elizabeth Hospital | Kowloon | 150001 | Hong Kong |
| Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori | Meldola | Forli-cesena | 47014 | Italy |
| Azienda Ospedaliera San Gerardo di Monza | Monza | Monza E Brianza | 20052 | Italy |
| Centro di Riferimento Oncologico di Aviano | Aviano | Pordenone | 33081 | Italy |
| Azienda Ospedaliera San Giuseppe Moscati | Avellino | 83100 | Italy |
| Istituto Oncologico di Bari Giovanni Paolo II | Bari | 70124 | Italy |
| Azienda Ospedaliero Universitaria di Bologna Policlinico Sant'Orsola-Malpighi | Bologna | 40138 | Italy |
| Istituto Scientifico Universitario San Raffaele | Milan | 20132 | Italy |
| Istituto Europeo di Oncologia | Milan | 20141 | Italy |
| Istituto Tumori Napoli Fondazione G. Pascale | Naples | 80131 | Italy |
| Azienda Ospedaliero Universitaria Maggiore della Carita | Novara | 28100 | Italy |
| Azienda Ospedaliera di Perugia - Ospedale S. Maria della Misericordia | Perugia | 06132 | Italy |
| Azienda Unita Sanitaria Locale di Ravenna | Ravenna | 48121 | Italy |
| Policlinico Universitario Campus Bio-Medico | Roma | 00128 | Italy |
| Centre Hospitalier de Luxembourg - Hopital Municipal | Luxembourg | 1210 | Luxembourg |
| Amphia Ziekenhuis - Locatie Langendijk Breda | Breda | North Brabant | 4818 CK | Netherlands |
| Antoni van Leeuwenhoekziekenhuis | Amsterdam | North Holland | 1066 CX | Netherlands |
| Isala Klinieken | Zwolle | Overijssel | 8025 AB | Netherlands |
| Universitair Medisch Centrum Groningen | Groningen | 9713 GZ | Netherlands |
| Radiumhospitalet | Oslo | 0379 | Norway |
| National University Hospital | Singapore | 119228 | Singapore |
| National Cancer Centre Singapore | Singapore | 169610 | Singapore |
| OncoCare Cancer Centre | Singapore | 258499 | Singapore |
| National Cancer Center | Goyang-si | Gyeonggi-do | 10408 | South Korea |
| Seoul National University Bundang Hospital | Seongnam-si | Gyeonggi-do | 13620 | South Korea |
| Chungbuk National University Hospital | Cheongju-si | North Chungcheong | 28644 | South Korea |
| Seoul National University Hospital | Seoul | 03080 | South Korea |
| Severance Hospital | Seoul | 03722 | South Korea |
| Asan Medical Center | Seoul | 05505 | South Korea |
| Samsung Medical Center | Seoul | 06351 | South Korea |
| The Catholic University of Korea | Seoul | 06591 | South Korea |
| Hospital Universitari Germans Trias i Pujol | Badalona | Barcelona | 08916 | Spain |
| Hospital Universitario Puerta de Hierro - Majadahonda | Majadahonda | Madrid | 28222 | Spain |
| Hospital Universitario Central de Asturias | Oviedo | Principality of Asturias | 33011 | Spain |
| Hospital Teresa Herrera - Materno Infantil | A Coruña | 15006 | Spain |
| Hospital General Universitario de Alicante | Alicante | 03010 | Spain |
| Hospital Universitario Vall d'Hebron | Barcelona | 08035 | Spain |
| Hospital Ramon Y Cajal | Madrid | 28034 | Spain |
| Hospital Universitario La Paz | Madrid | 28046 | Spain |
| Hospital Regional Universitario Carlos Haya Malaga Instituto de Neurociencias Clinicas | Málaga | 29010 | Spain |
| Hospital Universitario Marques de Valdecilla | Santander | 39008 | Spain |
| Hospital Universitario Virgen del Rocio | Seville | 41013 | Spain |
| Hospital Clinico Universitario de Valencia | Valencia | 46010 | Spain |
| Karolinska Universitetssjukhuset | Stockholm | 171 76 | Sweden |
| University Hospital Zurich | Zurich | 8091 | Switzerland |
| National Cheng Kung University | Tainan | Taipei | 70403 | Taiwan |
| China Medical University Hospital | Taichung | 404 | Taiwan |
| Taichung Veterans General Hospital | Taichung | 40705 | Taiwan |
| National Taiwan University Hospital | Taipei | 100 | Taiwan |
| Taipei Veterans General Hospital | Taipei | 11217 | Taiwan |
| Leicester Royal Infirmary | Leicester | England | LE1 5WW | United Kingdom |
| University College London | London | England | NW1 2PG | United Kingdom |
| Guy's and Saint Thomas' NHS Foundation Trust | London | England | SE1 9RT | United Kingdom |
| Royal Marsden NHS Trust | London | England | SW3 6JJ | United Kingdom |
| Maidstone Hospital | Maidstone | England | ME16 9QQ | United Kingdom |
| The Christie NHS Foundation Trust | Manchester | England | M20 4BX | United Kingdom |
| Derived |
| Al Tawil A, McGrath S, Ristl R, Mansmann U. Addressing treatment switching in the ALTA-1L trial with g-methods: exploring the impact of model specification. BMC Med Res Methodol. 2024 Dec 20;24(1):314. doi: 10.1186/s12874-024-02437-6. |
| 32780660 | Derived | Camidge DR, Kim HR, Ahn MJ, Yang JCH, Han JY, Hochmair MJ, Lee KH, Delmonte A, Garcia Campelo MR, Kim DW, Griesinger F, Felip E, Califano R, Spira A, Gettinger SN, Tiseo M, Lin HM, Gupta N, Hanley MJ, Ni Q, Zhang P, Popat S. Brigatinib Versus Crizotinib in Advanced ALK Inhibitor-Naive ALK-Positive Non-Small Cell Lung Cancer: Second Interim Analysis of the Phase III ALTA-1L Trial. J Clin Oncol. 2020 Nov 1;38(31):3592-3603. doi: 10.1200/JCO.20.00505. Epub 2020 Aug 11. |
| 30280657 | Derived | Camidge DR, Kim HR, Ahn MJ, Yang JC, Han JY, Lee JS, Hochmair MJ, Li JY, Chang GC, Lee KH, Gridelli C, Delmonte A, Garcia Campelo R, Kim DW, Bearz A, Griesinger F, Morabito A, Felip E, Califano R, Ghosh S, Spira A, Gettinger SN, Tiseo M, Gupta N, Haney J, Kerstein D, Popat S. Brigatinib versus Crizotinib in ALK-Positive Non-Small-Cell Lung Cancer. N Engl J Med. 2018 Nov 22;379(21):2027-2039. doi: 10.1056/NEJMoa1810171. Epub 2018 Sep 25. |
| 28501139 | Derived | Gainor JF, Shaw AT. J-ALEX: alectinib versus crizotinib in ALK-positive lung cancer. Lancet. 2017 Jul 1;390(10089):3-4. doi: 10.1016/S0140-6736(17)31074-7. Epub 2017 May 10. No abstract available. |
| Randomized Phase: Crizotinib 250 mg BID |
Crizotinib 250 mg, tablets, twice daily (BID) in each 28-day cycle until disease progression, intolerable toxicity, consent withdrawal, or death (The median duration of exposure was 9.26 months). |
| FG002 | Crossover Phase: Brigatinib 90 mg QD/180 mg QD | Participants who experienced PD as assessed by the blinded Independent Review Committee (BIRC) or received radiotherapy to the brain while on 'Crizotinib 250 mg BID' therapy in Randomized Phase were crossed over. Following 10-day washout period, crossover participants received brigatinib 90 mg, tablets, orally, QD for first 7 days followed by 180 mg, tablets, orally, QD in each 28-day cycle up to end of the study (The median duration of exposure was 17.25 months). |
| Safety Analysis Set |
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| COMPLETED |
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| NOT COMPLETED |
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| Crossover Phase |
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Intent-to-treat (ITT) Population included all participants randomized to each regimen regardless of whether they tested ALK+, or whether they received study drug or adhered to the assigned dose.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Randomized Phase: Brigatinib 90 mg QD/180 QD | Brigatinib 90 mg, tablets, orally, QD for first 7 days followed by 180 mg, orally, QD, in each 28-day cycle until PD, intolerable toxicity, consent withdrawal, or death (The median duration of exposure was 34.86 months). |
| BG001 | Randomized Phase: Crizotinib 250 mg BID | Crizotinib 250 mg, tablets, BID in each 28-day cycle until disease progression, intolerable toxicity, consent withdrawal, or death (The median duration of exposure was 9.26 months). |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | 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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| Global Health Status/Quality of Life (QoL) | HRQoL:perceived quality of participant's life,includes self-reported multidimensional measures of physical,mental health.EORTC-QLQ-C30 contains 30 items across 5 functional scales(physical,role,cognitive,emotional,social),9 symptom scales(fatigue,nausea and vomiting,pain,dyspnea,sleep disturbance,appetite loss,constipation,diarrhea,financial difficulties),a global health status/QOL scale on 4 response levels(not at all,a little,quite a bit,very much),with 2 questions relying on a 7-point numeric rating scale.Raw scores converted into overall score of 0-100,lower scores indicate better QOL. | Number analyzed is number of participants with data available for global health status/QoL at Baseline. | Mean | Full Range | score on a scale |
|
| 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 | Progression-free Survival (PFS) | PFS as assessed by Blinded Independent Review Committee (BIRC), per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, was defined as the time interval from the date of randomization until the date of the first documented PD event. The data was censored for participants without a PFS event. | ITT Population included all participants randomized to each regimen regardless of whether they tested ALK+, or whether they received study drug or adhered to the assigned dose. | Posted | Median | 95% Confidence Interval | months | Up to end of study (Up to 56 months) |
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| Secondary | Confirmed Objective Response Rate (ORR) | ORR was defined as percentage of participants who achieved Complete response (CR) or Partial responses (PR) using Response Evaluation Criteria in Solid Tumors (RECIST) version (v). 1.1 criteria. CR is defined as disappearance of all extranodal target and non-target lesions. All pathological lymph nodes must have decreased to less than (<) 10 mm in short axis for target lesions and all lymph nodes must be non-pathological in size (<10 mm short axis), normalization of tumor marker level for non-target lesions. PR is at least a 30% decrease in SLD of target lesions, taking as reference baseline sum diameters. | ITT Population included all participants randomized to each regimen regardless of whether they tested ALK+, or whether they received study drug or adhered to the assigned dose. | Posted | Number | 95% Confidence Interval | percentage of participants | Baseline up to end of treatment (Up to 36 months) |
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| Secondary | Confirmed Intracranial ORR (iORR) | ORR was defined as percentage of participants who achieved CR or PR in the central nervous system (CNS) in randomized participants with intracranial CNS metastasis at baseline. CR is defined as disappearance of all extranodal target and non-target lesions. All pathological lymph nodes must have decreased to <10 mm in short axis for target lesions and all lymph nodes must be non-pathological in size (<10 mm short axis), normalization of tumor marker level for non-target lesions. PR is at least a 30% decrease in the SLD of target lesions, taking as reference the baseline sum diameters. | ITT Population included all participants randomized to each regimen regardless of whether they tested ALK+, or whether they received study drug or adhered to the assigned dose. Overall number of participants analyzed are the participants with data available for analyses. | Posted | Number | 95% Confidence Interval | percentage of participants | Baseline up to end of treatment (Up to 36 months) |
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| Secondary | Intracranial Progression Free Survival | Intracranial PFS as assessed by BIRC, is defined as the time from randomization until first CNS PD is documented, or death due to any cause. PD is SLD increased by at least 20% from the smallest value on study (including baseline, if that is the smallest), the SLD must also demonstrate an absolute increase of at least 5 mm, and unequivocal progression of existing non-target lesions. | ITT Population included all participants randomized to each regimen regardless of whether they tested ALK+, or whether they received study drug or adhered to the assigned dose. Overall number of participants analyzed are the participants with data available for analyses. | Posted | Median | 95% Confidence Interval | months | Baseline up to end of study (Up to 56 months) |
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| Secondary | Overall Survival (OS) | Overall survival is defined as the time from randomization until death due to any cause. | ITT Population included all participants randomized to each regimen regardless of whether they tested ALK+, or whether they received study drug or adhered to the assigned dose. | Posted | Median | 95% Confidence Interval | months | Baseline up to end of study (Up to 56 months) |
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| Secondary | Duration of Response (DOR) | Duration of response as assessed by BIRC, is defined as the time interval from the date that the criteria are first met for CR/PR (whichever is first recorded) until the first date that progressive disease (PD) is objectively documented. CR is defined as disappearance of all extranodal target and non-target lesions. All pathological lymph nodes must have decreased to <10 mm in short axis for target lesions and all lymph nodes must be non-pathological in size (<10 mm short axis), normalization of tumor marker level for non-target lesions. PR is at least a 30 % decrease in the SLD of target lesions, taking as reference the baseline sum diameters. PD is SLD increased by at least 20% from the smallest value on study (including baseline, if that is the smallest), the SLD must also demonstrate an absolute increase of at least 5 mm, and for non-target lesions, unequivocal progression of existing non-target lesions. | ITT Population included all participants randomized to each regimen regardless of whether they tested ALK+, or whether they received study drug or adhered to the assigned dose. Only responders were reported for this outcome measure. | Posted | Median | Full Range | months | Baseline up to end of study (Up to 56 months) |
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| Secondary | Time to Response (TTR) | Time to response as assessed by BIRC, assessment and is defined as the time interval from the date of randomization until the initial observation of CR or PR. CR is defined as disappearance of all extranodal target and non-target lesions. All pathological lymph nodes must have decreased to <10 mm in short axis for target lesions and all lymph nodes must be non-pathological in size (<10 mm short axis), normalization of tumor marker level for non-target lesions. PR is at least a 30% decrease in the SLD of target lesions, taking as reference the baseline sum diameters. | ITT Population included all participants randomized to each regimen regardless of whether they tested ALK+, or whether they received study drug or adhered to the assigned dose. Only responders were reported for this outcome measure. | Posted | Median | Full Range | months | Baseline up to end of treatment (Up to 36 months) |
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| Secondary | Disease Control Rate (DCR) | Disease control as assessed by BIRC, defined as percentage of randomized participants who have achieved CR, PR, or stable disease (SD) after randomization. CR defined as disappearance of all extranodal target and non-target lesions. All pathological lymph nodes must have decreased to <10 mm in short axis for target lesions and all lymph nodes must be non-pathological in size (<10 mm short axis), normalization of tumor marker level for non-target lesions. PR: at least a 30% decrease in SLD of target lesions, taking as reference baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. PD: SLD increased by at least 20% from the smallest value on study, SLD must also demonstrate an absolute increase of at least 5 mm, and unequivocal progression of existing non-target lesions. | ITT Population included all participants randomized to each regimen regardless of whether they tested ALK+, or whether they received study drug or adhered to the assigned dose. | Posted | Number | 95% Confidence Interval | percentage of participants | Baseline up to end of treatment (Up to 36 months) |
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| Secondary | Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) | An AE is any untoward medical occurrence in a participant. An AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product whether or not considered related to the medicinal product. Any worsening of a preexisting condition which is temporally associated with the use of the study drug (i.e., occurs after the first dose of study drug) is also an AE. TEAEs are defined as AEs starting/worsening on or after the first dose of study treatment and no later than the earliest of 30 days after the last dose of the treatment to which the participant was assigned, or the day before start of brigatinib therapy in crossover participant. | Treated Population included all participant who received at least 1 dose of study drug and served as basis of safety analysis. | Posted | Number | percentage of participants | From first dose up to 30 days after last dose of study drug (Up to approximately 37 months) |
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| Secondary | Change From Baseline in Global Health Status/Quality of Life as Assessed by EORTC QLQ-C30 (Version 3.0) | HRQoL: perceived quality of participant's life, includes self-reported multidimensional measures of physical and mental health. Patient-reported symptoms (PROs) and HRQoL will be collected by administering the european organisation for research and treatment of cancer (EORTC) quality of life (QLQ)-C30 questionnaire. EORTC-QLQ-C30 contains 30 items across 5 functional scales (physical, role, cognitive, emotional, and social), 9 symptom scales (fatigue, nausea and vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and financial difficulties) and a global health status/QOL scale. The 30 items have 4 response levels (not at all, a little, quite a bit, and very much), with 2 questions relying on a 7-point numeric rating scale. Raw scores are converted into overall score ranging from 0 to 100, where lower scores indicate better QOL. A negative change from Baseline indicates improvement. | ITT Population included all participants randomized to each regimen regardless of whether they tested ALK+, or whether they received study drug or adhered to the assigned dose. Overall number of participants analyzed are the participants with data available for analyses. | Posted | Mean | Standard Deviation | score on a scale | Baseline and Month 36 |
|
All-Cause Mortality - Up to 56 months; Serious and other adverse events - From first dose up to 30 days after last dose of study drug (Up to approximately 37 months)
All Cause-mortality: ITT Population included all participants randomized to each regimen regardless of whether they tested ALK+, or whether they received study drug or adhered to the assigned dose. Serious and other (Non-serious): Treated Population included all participants who received ≥1 dose of study drug and served as basis of safety analysis. Crossover Population included participants from 'Crizotinib 250 mg BID' who crossed over to brigatinib following BIRC-assessed PD.
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 | Randomized Phase: Brigatinib 90 mg QD/180 QD | Brigatinib 90 mg, tablets, orally, QD for first 7 days followed by 180 mg, orally, QD, in each 28-day cycle until PD, intolerable toxicity, consent withdrawal, or death (The median duration of exposure was 34.86 months). | 41 | 137 | 56 | 136 | 132 | 136 |
| EG001 | Randomized Phase: Crizotinib 250 mg BID | Crizotinib 250 mg, tablets, BID in each 28-day cycle until disease progression, intolerable toxicity, consent withdrawal, or death (The median duration of exposure was 9.26 months). | 29 | 138 | 53 | 137 | 135 | 137 |
| EG002 | Crossover Phase: Brigatinib 90 mg QD/180 mg QD | Participants who experienced PD as assessed by the BIRC or received radiotherapy to the brain while on 'Crizotinib 250 mg BID' therapy in Randomized Phase were crossed over. Following 10-day washout period, crossover participants received brigatinib 90 mg, tablets, orally, QD for first 7 days followed by 180 mg, tablets, orally, QD in each 28-day cycle up to end of the study (The median duration of exposure was 17.25 months). | 22 | 65 | 24 | 65 | 63 | 65 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pneumonia | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Lower Respiratory Tract Infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Urinary Tract Infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Appendicitis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Upper Respiratory Tract Infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Viral Infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Respiratory Tract Infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Cytomegalovirus Oesophagitis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Herpes Zoster | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Listeriosis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Pleural Infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Septic Shock | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Sinusitis Fungal | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Neoplasm Progression | 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 |
| |
| 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 |
| |
| Cancer Pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
| |
| Diffuse Large B-Cell Lymphoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
| |
| Invasive Breast Carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
| |
| Lung Adenocarcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
| |
| Lung Neoplasm Malignant | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
| |
| Ovarian Cancer Stage I | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
| |
| Squamous Cell Carcinoma Of Skin | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
| |
| Hodgkins Disease | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
| |
| Tumour Haemorrhage | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Disseminated Intravascular Coagulation | Blood and lymphatic system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Anaemia Macrocytic | Blood and lymphatic system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Gout | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Confusional State | Psychiatric disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Delirium | Psychiatric disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Seizure | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Balance Disorder | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Cerebrovascular Accident | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Cognitive Disorder | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Dysarthria | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Encephalopathy | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Memory Impairment | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Partial Seizures | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Peripheral Sensory Neuropathy | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Vocal Cord Paralysis | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Ischaemic Stroke | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Central Nervous System Lesion | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Vertigo Positional | Ear and labyrinth disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Atrial Fibrillation | Cardiac disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Pericardial Effusion | Cardiac disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Cardiac Tamponade | Cardiac disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Acute Myocardial Infarction | Cardiac disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Angina Pectoris | Cardiac disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Arrhythmia | Cardiac disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Bradycardia | Cardiac disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Myocardial Infarction | Cardiac disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Palpitations | Cardiac 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 |
| |
| Pleural Effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Interstitial Lung Disease | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Pneumonitis | 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 |
| |
| Pulmonary Oedema | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Respiratory Distress | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Acute Respiratory Failure | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Respiratory Failure | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Gastric Haemorrhage | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Inguinal Hernia | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Neutropenic Colitis | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Oesophageal Obstruction | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Abdominal Pain Lower | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Abdominal Pain Upper | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Ascites | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Large Intestine Perforation | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Oesophagitis Ulcerative | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Cholecystitis | Hepatobiliary disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Bile Duct Stone | Hepatobiliary disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Cholestasis | Hepatobiliary disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Hepatocellular Injury | Hepatobiliary disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Drug-Induced Liver Injury | Hepatobiliary disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Back Pain | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Muscular Weakness | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Arthritis | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Bone Pain | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Rotator Cuff Syndrome | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Acute Kidney Injury | Renal and urinary disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Urinary Retention | Renal and urinary disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Menorrhagia | Reproductive system and breast disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Mucosal Inflammation | General disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Multiple Organ Dysfunction Syndrome | General disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Sudden Death | General disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Non-Cardiac Chest Pain | General disorders | MedDRA 23.0 | Systematic Assessment |
| |
| General Physical Health Deterioration | General disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Alanine Aminotransferase Increased | Investigations | MedDRA 23.0 | Systematic Assessment |
| |
| Aspartate Aminotransferase Increased | Investigations | MedDRA 23.0 | Systematic Assessment |
| |
| C-Reactive Protein Increased | Investigations | MedDRA 23.0 | Systematic Assessment |
| |
| Lipase Increased | Investigations | MedDRA 23.0 | Systematic Assessment |
| |
| Transaminases Abnormal | Investigations | MedDRA 23.0 | Systematic Assessment |
| |
| Neutrophil Count Decreased | Investigations | MedDRA 23.0 | Systematic Assessment |
| |
| Platelet Count Decreased | Investigations | MedDRA 23.0 | Systematic Assessment |
| |
| Femoral Neck Fracture | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
| |
| Ligament Rupture | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
| |
| Brain Herniation | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
| |
| Spinal Fracture | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
| |
| Tibia Fracture | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
| |
| Toxicity To Various Agents | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
| |
| Aphasia | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Atypical Pneumonia | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Cardiac Failure | Cardiac disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Depressed Level Of Consciousness | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Disorientation | Psychiatric disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Gastroenteritis Viral | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Generalised Tonic-Clonic Seizure | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Hemiparesis | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Intestinal Obstruction | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Intracranial Tumour Haemorrhage | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
| |
| Performance Status Decreased | General disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Pyelonephritis Acute | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Covid-19 | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Salmonella Sepsis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Prostate Cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
| |
| Intraventricular Haemorrhage | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Respiratory Arrest | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Abdominal Pain | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Upper Respiratory Tract Infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Urinary Tract Infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Respiratory Tract Infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | 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 |
| |
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Hypercholesterolaemia | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Anxiety | Psychiatric 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 |
| |
| Dysgeusia | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Hypoaesthesia | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Taste Disorder | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Vision Blurred | Eye disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Photopsia | Eye disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Visual Impairment | Eye disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Bradycardia | Cardiac disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Sinus Bradycardia | Cardiac disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Deep Vein Thrombosis | Vascular 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 |
| |
| Productive Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Pleural Effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Nausea | 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 |
| |
| Abdominal Pain Upper | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Dry Mouth | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Gastrooesophageal Reflux Disease | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Dermatitis Acneiform | Skin and subcutaneous tissue 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 |
| |
| Eczema | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Back Pain | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
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| Muscle Spasms | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
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| Musculoskeletal Pain | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
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| Musculoskeletal Chest Pain | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
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| Pain In Extremity | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
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| Muscular Weakness | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 23.0 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA 23.0 | Systematic Assessment |
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| Asthenia | General disorders | MedDRA 23.0 | Systematic Assessment |
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| Oedema Peripheral | General disorders | MedDRA 23.0 | Systematic Assessment |
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| Non-Cardiac Chest Pain | General disorders | MedDRA 23.0 | Systematic Assessment |
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| Malaise | General disorders | MedDRA 23.0 | Systematic Assessment |
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| Influenza Like Illness | General disorders | MedDRA 23.0 | Systematic Assessment |
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| Peripheral Swelling | General disorders | MedDRA 23.0 | Systematic Assessment |
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| Blood Creatine Phosphokinase Increased | Investigations | MedDRA 23.0 | Systematic Assessment |
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| Aspartate Aminotransferase Increased | Investigations | MedDRA 23.0 | Systematic Assessment |
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| Alanine Aminotransferase Increased | Investigations | MedDRA 23.0 | Systematic Assessment |
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| Lipase Increased | Investigations | MedDRA 23.0 | Systematic Assessment |
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| Amylase Increased | Investigations | MedDRA 23.0 | Systematic Assessment |
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| Blood Alkaline Phosphatase Increased | Investigations | MedDRA 23.0 | Systematic Assessment |
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| Blood Cholesterol Increased | Investigations | MedDRA 23.0 | Systematic Assessment |
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| Blood Creatinine Increased | Investigations | MedDRA 23.0 | Systematic Assessment |
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| Electrocardiogram Qt Prolonged | Investigations | MedDRA 23.0 | Systematic Assessment |
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| Blood Lactate Dehydrogenase Increased | Investigations | MedDRA 23.0 | Systematic Assessment |
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| Gamma-Glutamyltransferase Increased | Investigations | MedDRA 23.0 | Systematic Assessment |
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| Neutrophil Count Decreased | Investigations | MedDRA 23.0 | Systematic Assessment |
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| Amylase Increased | Investigations | MedDRA 23.0 | Systematic Assessment |
| |
| Blood Insulin Increased | Investigations | MedDRA 23.0 | Systematic Assessment |
|
In general, Investigators may publish clinical data after the earlier of (i) publication by the Sponsor or (ii) 12 months following the abandonment, early termination or database lock; provided a copy of the publication provided to Sponsor at least 30 days ahead of publication, the Sponsor's confidential information is removed as may be requested by Sponsor and Investigator defers publication for up to 60 days in the event Sponsor provides notice that it intends to file a patent application.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Takeda | +1-877-825-3327 | TrialDisclosures@takeda.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jun 3, 2020 | Jul 27, 2021 | SAP_001.pdf |
| ID | Term |
|---|---|
| D002289 | Carcinoma, Non-Small-Cell Lung |
| D008175 | Lung Neoplasms |
| D002277 | Carcinoma |
| D002294 | Carcinoma, Squamous Cell |
| D018287 | Carcinoma, Large Cell |
| D000230 | Adenocarcinoma |
| ID | Term |
|---|---|
| D002283 | Carcinoma, Bronchogenic |
| D001984 | Bronchial Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D018307 | Neoplasms, Squamous Cell |
Not provided
Not provided
| ID | Term |
|---|---|
| C000598580 | brigatinib |
| D000077547 | Crizotinib |
| ID | Term |
|---|---|
| D010880 | Piperidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D000631 | Aminopyridines |
| D011725 | Pyridines |
Not provided
Not provided
| Physician Decision |
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| Site Terminated by Sponsor |
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| Hong Kong |
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| Singapore |
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| Korea, Republic Of |
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| Taiwan, Province Of China |
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| Austria |
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| Denmark |
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| France |
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| Germany |
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| Italy |
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| Luxembourg |
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| Netherlands |
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| Norway |
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| Spain |
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| Sweden |
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| Switzerland |
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| United Kingdom |
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| Canada |
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| United States |
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| OG002 | Crossover Phase: Brigatinib 90 mg QD/180 mg QD | Participants who experienced PD as assessed by the BIRC or received radiotherapy to the brain while on 'Crizotinib 250 mg BID' therapy in Randomized Phase were crossed over. Following 10-day washout period, crossover participants received brigatinib 90 mg, tablets, orally, QD for first 7 days followed by 180 mg, tablets, orally, QD in each 28-day cycle up to end of the study (The median duration of exposure was 17.25 months). |
|
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|
| OG002 | Crossover Phase: Brigatinib 90 mg QD/180 mg QD | Participants who experienced PD as assessed by the BIRC or received radiotherapy to the brain while on 'Crizotinib 250 mg BID' therapy in Randomized Phase were crossed over. Following 10-day washout period, crossover participants received brigatinib 90 mg, tablets, orally, QD for first 7 days followed by 180 mg, tablets, orally, QD in each 28-day cycle up to end of the study (The median duration of exposure was 17.25 months). |
|
|
|
| Crossover Phase: Brigatinib 90 mg QD/180 mg QD |
Participants who experienced PD as assessed by the BIRC or received radiotherapy to the brain while on 'Crizotinib 250 mg BID' therapy in Randomized Phase were crossed over. Following 10-day washout period, crossover participants received brigatinib 90 mg, tablets, orally, QD for first 7 days followed by 180 mg, tablets, orally, QD in each 28-day cycle up to end of the study (The median duration of exposure was 17.25 months). |
|
|
|
|
|
| Randomized Phase: Crizotinib 250 mg BID |
Crizotinib 250 mg, tablets, BID in each 28-day cycle until disease progression, intolerable toxicity, consent withdrawal, or death (The median duration of exposure was 9.26 months). |
| OG002 | Crossover Phase: Brigatinib 90 mg QD/180 mg QD | Participants who experienced PD as assessed by the BIRC or received radiotherapy to the brain while on 'Crizotinib 250 mg BID' therapy in Randomized Phase were crossed over. Following 10-day washout period, crossover participants received brigatinib 90 mg, tablets, orally, QD for first 7 days followed by 180 mg, tablets, orally, QD in each 28-day cycle up to end of the study (The median duration of exposure was 17.25 months). |
|
|
| OG002 | Crossover Phase: Brigatinib 90 mg QD/180 mg QD | Participants who experienced PD as assessed by the BIRC or received radiotherapy to the brain while on 'Crizotinib 250 mg BID' therapy in Randomized Phase were crossed over. Following 10-day washout period, crossover participants received brigatinib 90 mg, tablets, orally, QD for first 7 days followed by 180 mg, tablets, orally, QD in each 28-day cycle up to end of the study (The median duration of exposure was 17.25 months). |
|
|
Crizotinib 250 mg, tablets, BID in each 28-day cycle until disease progression, intolerable toxicity, consent withdrawal, or death (The median duration of exposure was 9.26 months).
| OG002 | Crossover Phase: Brigatinib 90 mg QD/180 mg QD | Participants who experienced PD as assessed by the BIRC or received radiotherapy to the brain while on 'Crizotinib 250 mg BID' therapy in Randomized Phase were crossed over. Following 10-day washout period, crossover participants received brigatinib 90 mg, tablets, orally, QD for first 7 days followed by 180 mg, tablets, orally, QD in each 28-day cycle up to end of the study (The median duration of exposure was 17.25 months). |
|
|
|
| OG002 | Crossover Phase: Brigatinib 90 mg QD/180 mg QD | Participants who experienced PD as assessed by the BIRC or received radiotherapy to the brain while on 'Crizotinib 250 mg BID' therapy in Randomized Phase were crossed over. Following 10-day washout period, crossover participants received brigatinib 90 mg, tablets, orally, QD for first 7 days followed by 180 mg, tablets, orally, QD in each 28-day cycle up to end of the study (The median duration of exposure was 17.25 months). |
|
|
| OG001 | Randomized Phase: Crizotinib 250 mg BID | Crizotinib 250 mg, tablets, BID in each 28-day cycle until disease progression, intolerable toxicity, consent withdrawal, or death (The median duration of exposure was 9.26 months). |
|
|
|