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

NCT03596866 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: Brigatinib-30012018-001957-29
• Study Type: interventional
• Target: 248
• Locations: 20 countries
• Sites: 114

Brief Summary

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.

Conditions

ALK+ Advanced NSCLC

Keywords

Drug Therapy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (10)

• Overall Survival (OS)

  Up to 64 months

• PFS as Assessed by Investigator Per RECIST v1.1

  Up to 33.8 months

• Objective Response Rate (ORR) as Assessed by BIRC and Investigator Per RECIST v1.1

  Up to 33.8 months

• Duration of Response (DOR) as Assessed by BIRC and Investigator Per RECIST v1.1

  Up to 33.8 months

• Time to Response as Assessed by Investigator and BIRC Per RECIST v1.1

  Up to 33.8 months

Study Arms (2)

Brigatinib

EXPERIMENTAL

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

Alectinib

ACTIVE COMPARATOR

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

Interventions

Brigatinib DRUG

Brigatinib Tablets.

Also known as: Alunbrig

Brigatinib

Alectinib DRUG

Alectinib Capsules.

Also known as: Alecensa

Alectinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
• Have histologically or cytologically confirmed stage IIIB (locally advanced or recurrent) or stage IV NSCLC.
• 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).
• 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).
• Treatment with crizotinib for at least 4 weeks before progression except for participants previously participating in the Brigatinib-2002 study.
• Have had no other ALK inhibitor other than crizotinib except for participants previously participating in the Brigatinib-2002 study.
• 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).
• Have at least 1 measurable (that is, target) lesion per RECIST v1.1.
• 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).
• 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.

You may not qualify if:

• Had participated in the control (crizotinib) arm of Study AP26113-13-301 (ALTA 1L) \[NCT02737501\].
• Had received crizotinib within 7 days before randomization.
• Have a history or presence at baseline of pulmonary interstitial disease, drug related pneumonitis, or radiation pneumonitis.
• Have uncontrolled hypertension. Participants with hypertension should be under treatment for control of blood pressure upon study entry.
• 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.
• Treatment with any investigational systemic anticancer agents within 14 days or 5 half-lives, whichever is longer, before randomization.
• 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.
• Had received chemotherapy or radiation therapy within 14 days before randomization except for stereotactic radiosurgery (SRS) or stereotactic body radiation therapy.
• Had received antineoplastic monoclonal antibodies within 30 days of randomization.
• Had major surgery within 30 days of randomization. Minor surgical procedures, such as catheter placement or minimally invasive biopsies, are allowed.
• 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.
• Have current spinal cord compression (symptomatic or asymptomatic and detected by radiographic imaging). Participants with leptomeningeal disease and without cord compression are allowed.
• 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.

Sponsors & Collaborators

• Takeda: lead

Study Sites (114)

The Oncology Institute of Hope and Innovation

Whittier, California, 90602, United States

Location

University Cancer and Blood Center

Athens, Georgia, 30607, United States

Location

New York Oncology Hematology - Albany Medical Center

Albany, New York, 12208, United States

Location

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

Location

Centro Para la Atencion Integral del Paciente Oncologico

San Miguel de Tucumán, Tucumán Province, 4000, Argentina

Location

Sanatorio Duarte Quiros

Córdoba, 5000, Argentina

Location

Centro Oncologico Riojano Integral

La Rioja, F5300COE, Argentina

Location

Klinikum Klagenfurt Am Worthersee

Klagenfurt, Carinthia, 9020, Austria

Location

Queen Elizabeth II Health Sciences Centre

Halifax, Nova Scotia, B3H 1V7, Canada

Location

Toronto University Health Network

Toronto, Ontario, M5G 2M9, Canada

Location

Centro de Investigacion Clinica Bradford Hill

Recoleta, Santiago Metropolitan, 76894, Chile

Location

Beijing Chest Hospital

Beijing, Beijing Municipality, 100000, China

Location

Peking Union Medical College Hospital - East

Beijing, Beijing Municipality, 100032, China

Location

Peking University Cancer Hospital/Beijing Cancer Hospital

Beijing, Beijing Municipality, 100036, China

Location

The 307th Hospital of Chinese Peoples Liberation Army

Beijing, Beijing Municipality, 100071, China

Location

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100142, China

Location

The First Affiliated Hospital of Guangzhou Medical University

Guangzhou, Guangdong, 510120, China

Location

Affiliated Tumor Hospital of Harbin Medical University - The 3rd Affiliated Hospital of HMU

Harbin, Heilongjiang, 150081, China

Location

Henan Cancer Hospital

Zhengzhou, Henan, 450008, China

Location

Jilin Provincial Cancer Hospital (Changchun Cancer Hospital)

Changchun, Jilin, 13000, China

Location

Shanghai Chest Hospital

Shanghai, Shanghai Municipality, 200030, China

Location

Chang Gung Memorial Hospital Linkou Branch

Tianjin, Tianjin Municipality, 300060, China

Location

Tianjin Medical University Cancer Institute & Hospital

Tianjin, Tianjin Municipality, 300060, China

Location

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, 310003, China

Location

The First Affiliated Hospital, Zhejiang University

Hangzhou, Zhejiang, 31000, China

Location

Fudan University Shanghai Cancer Center

Dubrovnik, Dubrovnik-Neretva County, 20 000, Croatia

Location

Opca bolnica Dubrovnik

Dubrovnik, Dubrovnik-Neretva County, 20 000, Croatia

Location

General Hospital Pula

Pula, 52100, Croatia

Location

Klinicki bolnicki centar Sestre milosrdnice

Zagreb, 10000, Croatia

Location

Klinika za Pulmologiju

Zagreb, 10000, Croatia

Location

Hopital Haut-Leveque

Pessac, Aquitaine, 33604, France

Location

Hopital Albert Michallon

Grenoble, Auvergne-Rhône-Alpes, 38043, France

Location

Centre Hospitalier Universitaire de Toulouse- Hopital Larrey

Toulouse, Midi-pyrenees, 31059, France

Location

Centre Hospitalier Le Mans

Le Mans, Pays de la Loire Region, 72037, France

Location

Centre Hospitalier Intercommunal Toulon - La Seyne Sur Mer

Toulon, Provence-Alpes-Côte d'Azur Region, 83056, France

Location

Centre Hospitalier Intercommunal de Creteil

Créteil, Île-de-France Region, 94010, France

Location

Fudan University Shanghai Cancer Center

Créteil, Île-de-France Region, 94010, France

Location

Hopital Foch

Suresnes, Île-de-France Region, 92151, France

Location

Gustave Roussy

Villejuif, Île-de-France Region, 94805, France

Location

Thoraxklinik Heidelberg

Heidelberg, Baden-Wurttemberg, 69126, Germany

Location

Asklepios Fachkliniken Munchen-Gauting

Gauting, Bavaria, 82131, Germany

Location

Klinikum Kempten-Oberallgau

Immenstadt im Allgäu, Bavaria, 87509, Germany

Location

University General Hospital of Athens Attikon

Athens, Attica, 12462, Greece

Location

Iaso General Hospital

Cholargós, Attica, 15562, Greece

Location

General Oncology Hospital of Kifisia Oi Agioi Anargiroi

Nea Kifissia, Attica, 14564, Greece

Location

Interbalkan Medical Center of Thessaloniki

Thessaloniki, Macedonia, 57001, Greece

Location

University General Hospital of Larissa

Larissa, Thessaly, 41110, Greece

Location

Sotiria General Hospital for Respiratory Diseases of Attica

Athens, 11527, Greece

Location

Pamela Youde Nethersole Eastern Hospital

Chai Wan, Eastern District, 999077, Hong Kong

Location

Humanity and Health Research Centre

Central, Hong Kong

Location

Queen Mary Hospital

Hong Kong, 00852, Hong Kong

Location

Queen Mary Hospital

Hong Kong, Hong Kong

Location

Hong Kong United Oncology Centre

Kowloon, Hong Kong

Location

Princess Margaret Hospital

Kowloon, Hong Kong

Location

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori

Meldola, Forli-cesena, 47014, Italy

Location

Centro di Riferimento Oncologico di Aviano

Aviano, Pordenone, 33081, Italy

Location

Azienda Ospedaliero Universitaria di Bologna Policlinico Sant'Orsola-Malpighi

Bologna, 40138, Italy

Location

Azienda Ospedaliera Universitaria San Martino

Genova, 16132, Italy

Location

Istituto Scientifico Universitario San Raffaele

Milan, 20132, Italy

Location

Istituto Nazionale Tumori IRCCS Fondazione Pascale

Napoli, 80131, Italy

Location

Ospedale Santa Maria delle Croci

Ravenna, 48121, Italy

Location

Medica Sur

Mexico City, Mexico City, 14050, Mexico

Location

Centro de Investigacion Medica Aguascalientes

Aguascalientes, 20116, Mexico

Location

Institutul Oncologic Prof. Dr. Ion Chiricu

Cluj-Napoca, Cluj, 400015, Romania

Location

Oncocenter- Oncologie Clinica

Timișoara, Timiș County, 300166, Romania

Location

Institutul Oncologic Prof. Dr. Alexandru Trestioreanu Bucaresti

Bucharest, 022328, Romania

Location

Centrul de oncologie Euroclinic

Iași, 700106, Romania

Location

State Institution of Healthcare Arkhangelsk Regional Clinical Oncology Dispensary

Arkhangelsk, Arkhangelr, 163045, Russia

Location

Euromedservice

Saint Petersburg, Sankt-Peterburg, 196603, Russia

Location

Saint Petersburg Clinical Scientific and Practical Center of Specialized Types of Medical Aid

Saint Petersburg, Sankt-Peterburg, 197758, Russia

Location

Clinica Ultra Sound Diagnostic 4D

Pyatigorsk, Stavropol Kray, 357502, Russia

Location

Irkutsk Regional Oncology Center

Irkutsk, 664035, Russia

Location

N.N. Blokhin Russian Cancer Research Center

Moscow, 115478, Russia

Location

VitaMed

Moscow, 121309, Russia

Location

State Budget Institution National Medical Research Center of Radiology of the Ministry of Heal

Moscow, 125284, Russia

Location

Moscow City Oncology Hospital Number 62

Moscow, 143423, Russia

Location

Omsk Regional Clinical Oncologic Dispensary

Omsk, 644013, Russia

Location

Leningrad Regional Clinical Hospital

Saint Petersburg, 194291, Russia

Location

Center of Palliative Medicine - Devita

Saint Petersburg, 197343, Russia

Location

Saint Petersburg State Healthcare Institution Municipal Clinical Oncology Dispensary

Saint Petersburg, 197758, Russia

Location

National Cancer Center

Goyang-si, Gyeonggi-do, 10408, South Korea

Location

Gachon University Gil Medical Center

Incheon, Gyeonggi-do, 21565, South Korea

Location

The Catholic University of Korea St. Vincent's Hospital

Suwon, Gyeonggi-do, 16247, South Korea

Location

Ajou University Hospital

Suwon, Gyeonggi-do, 16499, South Korea

Location

Ulsan University Hospital

Ulsan, Gyeongsangnam-do, 44033, South Korea

Location

Chungbuk National University Hospital

Cheongju-si, North Chungcheong, 28644, South Korea

Location

Korea University Anam Hospital

Seoul, 02841, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

The Catholic University of Korea - Seoul St. Mary's Hospital

Seoul, 06591, South Korea

Location

Hospital Universitari Germans Trias i Pujol

Badalona, Barcelona, 08916, Spain

Location

Hospital Teresa Herrera - Materno Infantil

A Coruña, LA Coruna, 15006, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Clinic i Provincial de Barcelona

Barcelona, 08036, Spain

Location

Hospital General Universitario Gregorio Maranon

Madrid, 28007, Spain

Location

Hospital Universitario Ramon Y Cajal

Madrid, 28034, Spain

Location

Hospital Clinico San Carlos

Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Regional Universitario de Malaga

Málaga, 29010, Spain

Location

Hospital Universitari Sant Joan de Reus

Reus, 43204, Spain

Location

Hospital Universitario Virgen Macarena

Seville, 41009, Spain

Location

Karolinska Universitetssjukhuset - Solna

Solna, Stockholm County, 171 64, Sweden

Location

Uppsala Akademiska Sjukhus

Uppsala, 751 85, Sweden

Location

Changhua Christian Hospital

Changhua, 500, Taiwan

Location

Hualien Tzu Chi Hospital

Hualien City, 970, Taiwan

Location

Kaohsiung Medical University Hospital

Kaohsiung City, 807, Taiwan

Location

National Cheng Kung University Hospital

Tainan, 70403, Taiwan

Location

Chi Mei Hospital Liouying

Tainan, 73657, Taiwan

Location

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

Chang Gung Memorial Hospital Linkou Branch

Taoyuan, 333, Taiwan

Location

King Chulalongkorn Memorial Hospital

Bangkok, Bangkok Metropolis, 10330, Thailand

Location

Phramongkutklao Hospital

Bangkok, Bangkok Metropolis, 10400, Thailand

Location

Songklanagarind Hospital

Songkhla, 90110, Thailand

Location

Related Publications (2)

• 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.

  PMID: 37574132 DERIVED

• 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.

  PMID: 34423676 DERIVED

Related Links

• Related Info

MeSH Terms

Interventions

brigatinib; alectinib

Results Point of Contact

• Title: Study Director
• Organization: Takeda

TrialDisclosures@takeda.com

+1-877-825-3327

Study Officials

• Medical Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 13, 2018
• First Posted: July 24, 2018
• Study Start: April 19, 2019
• Primary Completion: February 27, 2024
• Study Completion: September 18, 2024
• Last Updated: September 12, 2025
• Results First Posted: February 19, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• 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.

Locations

SE (2); CR (5); TH (3); ME (2); US (4); GR (6); RU (13); ES (12); IT (7); AU (1); CN (14); HK (6); RO (4); TW (7); CA (2); KR (10); FR (9); AR (3); DE (3); CL (1)