A Study of Brigatinib Compared to Alectinib in Adults With Non-Small-Cell Lung Cancer (ALTA-3)

A Phase 3 Randomized Open-label Study of Brigatinib (ALUNBRIG®) Versus Alectinib (ALECENSA®) in Advanced Anaplastic Lymphoma Kinase-Positive Non-Small-Cell Lung Cancer Patients Who Have Progressed on Crizotinib (XALKORI®)

Brigatinib is a medicine that binds to the surface of tumor cells in some cancers and delivers a dose of chemotherapy directly to the tumor. In this study, participants will be people with non-small-cell lung cancer (NSCLC for short). The main aim of the study is to learn if brigatinib stops the tumors from growing, or if the tumors have shrunk or disappeared, compared to a medicine called alectinib.

At the first visit, the study doctor will check who can take part. Participants who can take part will be picked for 1 of 2 treatments by chance:

• Brigatinib tablets
• Alectinib capsules

All participants will take brigatinib or alectinib at about the same time every day. They will continue with treatment throughout the study unless their cancer gets worse, they have side effects from the treatment, they leave the study for certain reasons, or the study is stopped.

After stopping treatment, participants will visit the study clinic for a check-up 30 days later.

Study Overview

• Status: Completed
• Conditions: ALK+ Advanced NSCLC
• Intervention / Treatment: Drug: Brigatinib; Drug: Alectinib

Detailed Description

The drug being tested in this study is called brigatinib. Brigatinib has been demonstrated to benefit people with anaplastic lymphoma kinase-positive (ALK+) NSCLC.

The comparator drug is called alectinib. Alectinib has been demonstrated to benefit people with ALK+ NSCLC. Both drugs belong to a class of drugs called anaplastic lymphoma kinase (ALK) inhibitors. Both drugs are taken by mouth. Both drugs are approved by the United States Food and Drug Administration (US FDA).

The study will enroll approximately 246 participants. Participants will be randomly assigned (by chance, like flipping a coin) in 1:1 ratio to one of the two treatment groups:

• Brigatinib
• Alectinib

All participants will be asked to take brigatinib or alectinib at the same time each day throughout the study. For each participant eligible to continue in the study and to facilitate the remaining participants from Brigatinib-2002 (NCT03535740) to have continued treatment access, the study extension phase may be initiated for participants to continue receiving their randomized study treatment (i.e., brigatinib or alectinib) until they meet at least one of the treatment discontinuation criteria.

This multi-center trial will be conducted in the United States, Argentina, Austria, Canada, Chile, China, Croatia, France, Germany, Greece, Hong Kong, Italy, Mexico, Romania, Russia, South Korea, Spain, Sweden, Taiwan, and Thailand. The overall time to participate in this study is 5 years. Participants will make multiple visits to the clinic, and 30 days after last dose of study drug for a follow-up assessment.

• Study Type: Interventional
• Enrollment (Actual): 248
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Córdoba, Argentina, 5000
    • Sanatorio Duarte Quirós
  • La Rioja, Argentina, F5300COE
    • Centro Oncologico Riojano Integral
  • Tucumán Province
    • San Miguel de Tucumán, Tucumán Province, Argentina, 4000
      • Centro para la Atención Integral del paciente Oncológico
• Austria
  • Carinthia
    • Klagenfurt, Carinthia, Austria, 9020
      • Klinikum Klagenfurt am Wörthersee
• Canada
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1V7
      • Queen Elizabeth II Health Sciences Centre
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Toronto University Health Network
• Chile
  • Santiago Metropolitan
    • Recoleta, Santiago Metropolitan, Chile, 76894
      • Centro de Investigacion Clinica Bradford Hill
• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100142
      • Beijing Cancer Hospital
    • Beijing, Beijing Municipality, China, 100000
      • Beijing Chest Hospital
    • Beijing, Beijing Municipality, China, 100032
      • Peking Union Medical College Hospital - East
    • Beijing, Beijing Municipality, China, 100036
      • Peking University Cancer Hospital/Beijing Cancer Hospital
    • Beijing, Beijing Municipality, China, 100071
      • The 307th Hospital of Chinese Peoples Liberation Army
  • Guangdong
    • Guangzhou, Guangdong, China, 510120
      • The First Affiliated Hospital of Guangzhou Medical University
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150081
      • Affiliated Tumor Hospital of Harbin Medical University - The 3rd Affiliated Hospital of HMU
  • Henan
    • Zhengzhou, Henan, China, 450008
      • Henan Cancer Hospital
  • Jilin
    • Changchun, Jilin, China, 13000
      • Jilin Provincial Cancer Hospital (Changchun Cancer Hospital)
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200030
      • Shanghai Chest Hospital
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China, 300060
      • Tianjin Medical University Cancer Institute & Hospital
    • Tianjin, Tianjin Municipality, China, 300060
      • Chang Gung Memorial Hospital Linkou Branch
  • Zhejiang
    • Hangzhou, Zhejiang, China, 31000
      • The First Affiliated Hospital, Zhejiang University
    • Hangzhou, Zhejiang, China, 310003
      • Zhejiang Cancer Hospital
• Croatia
  • Pula, Croatia, 52100
    • General Hospital Pula
  • Zagreb, Croatia, 10000
    • Klinički Bolnički Centar Sestre Milosrdnice
  • Zagreb, Croatia, 10000
    • Klinika za Pulmologiju
  • Dubrovnik-Neretva County
    • Dubrovnik, Dubrovnik-Neretva County, Croatia, 20 000
      • Fudan University Shanghai Cancer Center
    • Dubrovnik, Dubrovnik-Neretva County, Croatia, 20 000
      • Opća bolnica Dubrovnik
• France
  • Aquitaine
    • Pessac, Aquitaine, France, 33604
      • Hôpital Haut-Lévêque
  • Midi-pyrenees
    • Toulouse, Midi-pyrenees, France, 31059
      • Centre Hospitalier Universitaire de Toulouse- Hopital Larrey
  • Pays de la Loire Region
    • Le Mans, Pays de la Loire Region, France, 72037
      • Centre Hospitalier Le Mans
  • Provence-Alpes-Côte d'Azur Region
    • Toulon, Provence-Alpes-Côte d'Azur Region, France, 83056
      • Centre Hospitalier Intercommunal Toulon - La Seyne sur Mer
  • Rhone-alpes
    • Grenoble, Rhone-alpes, France, 38043
      • Hôpital Albert Michallon
  • Île-de-France Region
    • Créteil, Île-de-France Region, France, 94010
      • Centre Hospitalier Intercommunal de Creteil
    • Créteil, Île-de-France Region, France, 94010
      • Fudan University Shanghai Cancer Center
    • Suresnes, Île-de-France Region, France, 92151
      • Hopital Foch
    • Villejuif, Île-de-France Region, France, 94805
      • Gustave Roussy
• Germany
  • Baden-Wurttemberg
    • Heidelberg, Baden-Wurttemberg, Germany, 69126
      • Thoraxklinik Heidelberg
  • Bavaria
    • Gauting, Bavaria, Germany, 82131
      • Asklepios Fachkliniken München-Gauting
    • Immenstadt im Allgäu, Bavaria, Germany, 87509
      • Klinikum Kempten-Oberallgäu
• Greece
  • Athens, Greece, 11527
    • Sotiria General Hospital for Respiratory Diseases of Attica
  • Attica
    • Athens, Attica, Greece, 12462
      • University General Hospital of Athens Attikon
    • Cholargós, Attica, Greece, 15562
      • IASO general hospital
    • Nea Kifissia, Attica, Greece, 14564
      • General Oncology Hospital of Kifisia Oi Agioi Anargiroi
  • Macedonia
    • Thessaloniki, Macedonia, Greece, 57001
      • Interbalkan Medical Center of Thessaloniki
  • Thessaly
    • Larissa, Thessaly, Greece, 41110
      • University General Hospital of Larissa
• Hong Kong
  • Central, Hong Kong
    • Humanity and Health Research Centre
  • Hong Kong, Hong Kong
    • Queen Mary Hospital
  • Hong Kong, Hong Kong, 00852
    • Queen Mary Hospital
  • Kowloon, Hong Kong
    • Princess Margaret Hospital
  • Kowloon, Hong Kong
    • Hong Kong United Oncology Centre
  • Eastern District
    • Chai Wan, Eastern District, Hong Kong, 999077
      • Pamela Youde Nethersole Eastern Hospital
• Italy
  • Bologna, Italy, 40138
    • Azienda Ospedaliero Universitaria di Bologna Policlinico Sant'Orsola-Malpighi
  • Genova, Italy, 16132
    • Azienda Ospedaliera Universitaria San Martino
  • Milan, Italy, 20132
    • Istituto Scientifico Universitario San Raffaele
  • Napoli, Italy, 80131
    • Istituto Nazionale Tumori IRCCS Fondazione Pascale
  • Ravenna, Italy, 48121
    • Ospedale Santa Maria delle Croci
  • Forli-cesena
    • Meldola, Forli-cesena, Italy, 47014
      • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
  • Pordenone
    • Aviano, Pordenone, Italy, 33081
      • Centro di Riferimento Oncologico di Aviano
• Mexico
  • Aguascalientes, Mexico, 20116
    • Centro de Investigacion Medica Aguascalientes
  • Mexico City
    • Mexico City, Mexico City, Mexico, 14050
      • Médica Sur
• Romania
  • Bucharest, Romania, 022328
    • Institutul Oncologic Prof. Dr. Alexandru Trestioreanu Bucaresti
  • Iași, Romania, 700106
    • Centrul de Oncologie Euroclinic
  • Cluj
    • Cluj-Napoca, Cluj, Romania, 400015
      • Institutul Oncologic Prof. Dr. Ion Chiricu
  • Timiș County
    • Timișoara, Timiș County, Romania, 300166
      • Oncocenter- Oncologie Clinica
• Russia
  • Irkutsk, Russia, 664035
    • Irkutsk Regional Oncology Center
  • Moscow, Russia, 115478
    • N.N. Blokhin Russian Cancer Research Center
  • Moscow, Russia, 121309
    • VitaMed
  • Moscow, Russia, 125284
    • State Budget Institution National Medical Research Center of Radiology of the Ministry of Heal
  • Moscow, Russia, 143423
    • Moscow City Oncology Hospital Number 62
  • Omsk, Russia, 644013
    • Omsk Regional Clinical Oncologic Dispensary
  • Saint Petersburg, Russia, 194291
    • Leningrad Regional Clinical Hospital
  • Saint Petersburg, Russia, 197343
    • Center of Palliative Medicine - Devita
  • Saint Petersburg, Russia, 197758
    • Saint Petersburg State Healthcare Institution Municipal Clinical Oncology Dispensary
  • Arkhangelr
    • Arkhangelsk, Arkhangelr, Russia, 163045
      • State Institution of Healthcare Arkhangelsk Regional Clinical Oncology Dispensary
  • Sankt-Peterburg
    • Saint Petersburg, Sankt-Peterburg, Russia, 196603
      • Euromedservice
    • Saint Petersburg, Sankt-Peterburg, Russia, 197758
      • Saint Petersburg Clinical Scientific and Practical Center of Specialized Types of Medical Aid
  • Stavropol Kray
    • Pyatigorsk, Stavropol Kray, Russia, 357502
      • Clinica Ultra Sound Diagnostic 4D
• South Korea
  • Seoul, South Korea, 03080
    • Seoul National University Hospital
  • Seoul, South Korea, 06351
    • Samsung Medical Center
  • Seoul, South Korea, 02841
    • Korea University Anam Hospital
  • Seoul, South Korea, 06591
    • The Catholic University of Korea - Seoul St. Mary's Hospital
  • Gyeonggi-do
    • Goyang-si, Gyeonggi-do, South Korea, 10408
      • National Cancer Center
    • Incheon, Gyeonggi-do, South Korea, 21565
      • Gachon University Gil Medical Center
    • Suwon, Gyeonggi-do, South Korea, 16499
      • Ajou University Hospital
    • Suwon, Gyeonggi-do, South Korea, 16247
      • The Catholic University Of Korea St. Vincent's Hospital
  • Gyeongsangnam-do
    • Ulsan, Gyeongsangnam-do, South Korea, 44033
      • Ulsan University Hospital
  • North Chungcheong
    • Cheongju-si, North Chungcheong, South Korea, 28644
      • Chungbuk National University Hospital
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain, 08036
    • Hospital Clinic i Provincial de Barcelona
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain, 28040
    • Hospital Clinico San Carlos
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañon
  • Málaga, Spain, 29010
    • Hospital Regional Universitario de Malaga
  • Reus, Spain, 43204
    • Hospital Universitari Sant Joan de Reus
  • Seville, Spain, 41009
    • Hospital Universitario Virgen Macarena
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Hospital Universitari Germans Trias i Pujol
  • LA Coruna
    • A Coruña, LA Coruna, Spain, 15006
      • Hospital Teresa Herrera - Materno Infantil
• Sweden
  • Uppsala, Sweden, 751 85
    • Uppsala Akademiska Sjukhus
  • Stockholm County
    • Solna, Stockholm County, Sweden, 171 64
      • Karolinska Universitetssjukhuset - Solna
• Taiwan
  • Changhua, Taiwan, 500
    • Changhua Christian Hospital
  • Hualien City, Taiwan, 970
    • Hualien Tzu Chi Hospital
  • Kaohsiung City, Taiwan, 807
    • Kaohsiung Medical University Hospital
  • Tainan City, Taiwan, 73657
    • Chi Mei Hospital Liouying
  • Tainan City, Taiwan, 70403
    • National Cheng Kung University Hospital
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital
  • Taoyuan, Taiwan, 333
    • Chang Gung Memorial Hospital Linkou Branch
• Thailand
  • Songkhla, Thailand, 90110
    • Songklanagarind Hospital
  • Bangkok Metropolis
    • Bangkok, Bangkok Metropolis, Thailand, 10330
      • King Chulalongkorn Memorial Hospital
    • Bangkok, Bangkok Metropolis, Thailand, 10400
      • Phramongkutklao Hospital
• United States
  • California
    • Whittier, California, United States, 90602
      • The Oncology Institute of Hope and Innovation
  • Georgia
    • Athens, Georgia, United States, 30607
      • University Cancer and Blood Center
  • New York
    • Albany, New York, United States, 12208
      • New York Oncology Hematology - Albany Medical Center
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
2. Have histologically or cytologically confirmed stage IIIB (locally advanced or recurrent) or stage IV NSCLC.

3. Must meet one of the following criteria:

   • Have documentation of ALK rearrangement by a positive result from the Vysis ALK Break-Apart fluorescence in situ hybridization (FISH) Probe Kit or the Ventana ALK (D5F3) CDx Assay or Foundation Medicine's FoundationOne CDx.
   • Have documented ALK rearrangement by a different test and be able to provide tumor sample to the central laboratory. (Note: central laboratory ALK rearrangement testing results are not required to be obtained before randomization).
4. Had PD while on crizotinib, as assessed by the investigator or treating physician except for participants previously participating in the Brigatinib-2002 study (Note: crizotinib does not need to be the last therapy a participant received. The participant may have received chemotherapy as his/her last therapy).
5. Treatment with crizotinib for at least 4 weeks before progression except for participants previously participating in the Brigatinib-2002 study.
6. Have had no other ALK inhibitor other than crizotinib except for participants previously participating in the Brigatinib-2002 study.
7. Have had no more than 2 prior regimens of systemic anticancer therapy (other than crizotinib) in the locally advanced or metastatic setting. Note: a systemic anticancer therapy regimen will be counted if it is administered for at least 1 complete cycle. A new anticancer agent used as maintenance therapy will be counted as a new regimen. Neoadjuvant or adjuvant systemic anticancer therapy will be counted as a prior regimen if disease progression/recurrence occurred within 12 months upon completion of this neoadjuvant or adjuvant therapy. (Systemic therapy followed by maintenance therapy will be considered as one regimen if the maintenance therapy consists of a drug or drugs that were used in the regimen that immediately preceded maintenance).
8. Have at least 1 measurable (that is, target) lesion per RECIST v1.1.
9. Have recovered from toxicities related to prior anticancer therapy to national cancer institute common terminology criteria for adverse events (NCI CTCAE) version 4.03 grade less than or equal to (<=)1. (Note: treatment-related alopecia or peripheral neuropathy that are grade greater than (>) 1 are allowed, if deemed irreversible).

10. Have adequate organ function, at the time of initial screening, except for participants previously participating in the Brigatinib-2002 study as determined by:

    • Total bilirubin <=1.5 times the upper limit of normal (ULN).
    • Estimated glomerular filtration rate greater than equal to (>=) 30 milliliter per minute (mL/min)/1.73 square meter [m^2], using the modification of diet in renal disease equation.
    • Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) <=2.5*ULN; <=5*ULN is acceptable if liver metastases are present.
    • Serum lipase <=1.5*ULN.
    • Platelet count >=75*10^9 per liter [/L].
    • Hemoglobin >=9 gram per deciliter (g/dL).
    • Absolute neutrophil count >=1.5*10^9 / L.
11. Suitable venous access for study-required blood sampling (that is, including pharmacokinetic [PK] and laboratory safety tests).

Exclusion Criteria:

1. Had participated in the control (crizotinib) arm of Study AP26113-13-301 (ALTA 1L) [NCT02737501].
2. Had received crizotinib within 7 days before randomization.
3. Have a history or presence at baseline of pulmonary interstitial disease, drug related pneumonitis, or radiation pneumonitis.
4. Have uncontrolled hypertension. Participants with hypertension should be under treatment for control of blood pressure upon study entry.
5. Had received systemic treatment with strong cytochrome P-450 (CYP) 3A inhibitors, moderate CYP3A inhibitors, strong CYP3A inducers, or moderate CYP3A inducers within 14 days before randomization.
6. Treatment with any investigational systemic anticancer agents within 14 days or 5 half-lives, whichever is longer, before randomization.
7. Have been diagnosed with another primary malignancy other than NSCLC, except for adequately treated nonmelanoma skin cancer or cervical cancer in situ; definitively treated nonmetastatic prostate cancer; or participants with another primary malignancy who are definitively relapse-free with at least 3 years elapsed since the diagnosis of the other primary malignancy.
8. Had received chemotherapy or radiation therapy within 14 days before randomization except for stereotactic radiosurgery (SRS) or stereotactic body radiation therapy.
9. Had received antineoplastic monoclonal antibodies within 30 days of randomization.
10. Had major surgery within 30 days of randomization. Minor surgical procedures, such as catheter placement or minimally invasive biopsies, are allowed.
11. Have symptomatic CNS metastases (parenchymal or leptomeningeal) at screening (participants with asymptomatic brain metastases or participants who have stable symptoms and did not require an increased dose of corticosteroids to control symptoms within 7 days before randomization will be enrolled). Note: If a participant has worsening neurological symptoms or signs due to CNS metastasis, the participant needs to complete local therapy and be neurologically stable (with no requirement for an increasing dose of corticosteroids or use of anticonvulsants) for 7 days before randomization.
12. Have current spinal cord compression (symptomatic or asymptomatic and detected by radiographic imaging). Participants with leptomeningeal disease and without cord compression are allowed.

13. Have significant, uncontrolled, or active cardiovascular disease, specifically including, but not restricted to the following:

    • Myocardial infarction within 6 months before randomization.
    • Unstable angina within 6 months before randomization.
    • New York Heart Association Class III or IV heart failure within 6 months before randomization.
    • History of clinically significant atrial arrhythmia (including clinically significant bradyarrhythmia), as determined by the treating physician.
    • Any history of clinically significant ventricular arrhythmia.
14. Had cerebrovascular accident or transient ischemic attack within 6 months before first dose of study drug.
15. Have malabsorption syndrome or other gastrointestinal illness or condition that could affect oral absorption of the study drug.
16. Have an ongoing or active infection, including but not limited to, the requirement for intravenous antibiotics.
17. Have a known history of human immunodeficiency virus (HIV) infection. Testing is not required in the absence of history.
18. Known hepatitis B surface antigen-positive, or known or suspected active hepatitis C infection. Testing is not required in the absence of history.
19. Any serious medical condition or psychiatric illness that could, in the investigator's opinion, potentially compromise participant safety or interfere with the completion of treatment according to this protocol.
20. Have a known or suspected hypersensitivity to brigatinib or alectinib or their excipients.
21. Life-threatening illness unrelated to cancer.
22. Female participants who are lactating and breastfeeding.
23. Admission or evidence of illicit drug use, drug abuse, or alcohol abuse.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Brigatinib; Participants were administered brigatinib 90 milligrams (mg), tablets, orally, once daily (QD) for 7 days, followed by brigatinib 180 mg, tablets, orally, QD until objective disease progression per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), as assessed by the investigator, or intolerable toxicity, or up to 63.47 months.	Drug: Brigatinib; Brigatinib Tablets.; Other Names: Alunbrig
Active Comparator: Alectinib; Participants were administered alectinib 600 mg, capsules, orally, twice daily (BID) until objective disease progression per RECIST v1.1, as assessed by the investigator, or intolerable toxicity, or up to 59.83 months.	Drug: Alectinib; Alectinib Capsules.; Other Names: Alecensa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS) as Assessed by Blinded Independent Review Committee (BIRC) Per RECIST v1.1	PFS is defined as the time interval from the date of randomization until the first date at which disease progression is objectively documented via RECIST v1.1 by BIRC, or death due to any cause, whichever occurs first, in the full analysis set. PFS was censored for participants without documented disease progression or death at the last valid tumor response assessment.	Up to 33.8 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	OS is defined as the time interval from the date of randomization until death due to any cause in the full analysis set. OS was censored on the date of last contact for those participants who are alive.	Up to 64 months
PFS as Assessed by Investigator Per RECIST v1.1	PFS is defined as the time interval from the date of randomization until the first date at which disease progression is objectively documented via RECIST v1.1 by investigator, or death due to any cause, whichever occurs first, in the full analysis set. PFS was censored for participants without documented disease progression or death at the last valid tumor response assessment.	Up to 33.8 months
Objective Response Rate (ORR) as Assessed by BIRC and Investigator Per RECIST v1.1	ORR is defined as the percentage of the participants who are confirmed to have achieved complete response (CR) or partial response (PR), using RECIST v1.1 after the initiation of study treatment. Percentages were rounded off to the nearest single decimal place.	Up to 33.8 months
Duration of Response (DOR) as Assessed by BIRC and Investigator Per RECIST v1.1	DOR is defined as the time interval from the time that the measurement criteria are first met for CR or PR (whichever is first recorded) until the first date that the progressive disease (PD) is objectively documented or death, as assessed by the investigator and BIRC, using RECIST v1.1. Participants who did not progress or died, were censored at the last tumor assessment date prior to receiving subsequent anticancer therapy.	Up to 33.8 months
Time to Response as Assessed by Investigator and BIRC Per RECIST v1.1	Time to response is defined as the time interval from randomization until the initial observation of CR or PR, as assessed by the investigator and BIRC, using RECIST v1.1. Time to response will be summarized using descriptive statistics in participants with confirmed objective response.	Up to 33.8 months
Confirmed Intracranial Objective Response Rate (iORR) as Assessed by BIRC Per Modified RECIST v1.1	Confirmed iORR, as assessed by the BIRC, is defined as the percentage of the participants who have achieved CR or PR in the central nervous system (CNS) per a modification RECIST v1.1 after the initiation of study treatment in participants with CNS metastases at baseline. Percentages were rounded off to the nearest single decimal place.	Up to 33.8 months
Intracranial Duration of Response (iDOR) as Assessed by the BIRC Per Modified RECIST v1.1	iDOR, as assessed by the BIRC per modified RECIST v1.1, is defined as the time interval from the time that the measurement criteria are first met for CR or PR in the CNS (whichever is first recorded) until the first date that the PD in the CNS is objectively documented or death. Participants who did not progress or died, were censored at the last iCNS tumor assessment date prior to receiving subsequent anticancer therapy.	Up to 33.8 months
Cumulative Incidence of Intracranial Disease Progression (iPD) as Assessed by BIRC Per Modified RECIST v1.1	Time to iPD as assessed by the BIRC,is defined as time interval from date of randomization until first date at which iPD is objectively documented via a modification of RECIST v1.1 without prior systemic progression (PD) or death. Time to iPD was analyzed within a competing risk framework (with systemic progression and death as the competing risks) by estimating the cumulative incidence function (CIF) within each arm. The CIF is a function of time, and indicates the probability of an event (e.g. iPD without prior PD or death) occurring by the specified time. The estimated CIFs were analyzed using Grey's Test and the estimated probability of CIFs is reported at pre-specified landmark times (6, 12, 18 and 24 months).	6, 12, 18 and 24 months
Health-Related Quality of Life (HRQOL) From European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30 v3.0) Score	EORTC QLQ-C30 incorporates 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 1 global health status scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). EORTC QLQ-C30 contains 28 questions (4-point scale where 1=Not at all [best] to 4=Very Much [worst]) and 2 questions (7-point scale where 1=Very poor [worst] to 7= Excellent [best]). Raw scores are converted into scale scores ranging from 0 to 100. For the functional scales and the global health status scale, higher scores represent better quality of life (QOL); for the symptom scales, lower scores represent better QOL.	Up to 33.8 months
HRQOL From EORTC QLQ- Lung Cancer (LC) 13	HRQOL scores were assessed with European Organization for Research and Treatment (EORTC), its lung cancer module QLQ-LC13. QLQ-LC13 contains 13 questions assessing lung cancer-associated symptoms (cough, hemoptysis, dyspnea, and site-specific pain), treatment-related side effects (sore mouth, dysphagia, peripheral neuropathy, and alopecia), and use of pain medication. Subscales were scored on a range of 0 to 100. Higher symptom score = greater degree of symptom severity.	Up to 33.8 months

Collaborators and Investigators

• Sponsor: Takeda
• Investigators: Study Director: Medical Director, Takeda

Publications and helpful links

General Publications

• Popat S, Liu G, Lu S, Song G, Ma X, Yang JC. Brigatinib vs alectinib in crizotinib-resistant advanced anaplastic lymphoma kinase-positive non-small-cell lung cancer (ALTA-3). Future Oncol. 2021 Nov;17(32):4237-4247. doi: 10.2217/fon-2021-0608. Epub 2021 Aug 23.
• Yang JC, Liu G, Lu S, He J, Burotto M, Ahn MJ, Kim DW, Liu X, Zhao Y, Vincent S, Yin J, Ma X, Lin HM, Popat S. Brigatinib Versus Alectinib in ALK-Positive NSCLC After Disease Progression on Crizotinib: Results of Phase 3 ALTA-3 Trial. J Thorac Oncol. 2023 Dec;18(12):1743-1755. doi: 10.1016/j.jtho.2023.08.010. Epub 2023 Aug 12.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): April 19, 2019
• Primary Completion (Actual): February 27, 2024
• Study Completion (Actual): September 18, 2024

Study Registration Dates

• First Submitted: July 13, 2018
• First Submitted That Met QC Criteria: July 13, 2018
• First Posted (Actual): July 24, 2018

Study Record Updates

• Last Update Posted (Estimated): September 12, 2025
• Last Update Submitted That Met QC Criteria: September 11, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Drug Therapy
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Tyrosine Kinase Inhibitors; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; alectinib; brigatinib
• Other Study ID Numbers: Brigatinib-3001; 2018-001957-29 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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.
• IPD Sharing Access Criteria: 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No