A Study of Brigatinib in Participants With Anaplastic Lymphoma Kinase-Positive (ALK+), Advanced Non-Small-Cell Lung Cancer (NSCLC) Progressed on Alectinib or Ceritinib

NCT03535740 | Completed Phase 2 Results FDA Drug

• 4 other identifiers: Brigatinib-20022018-000635-27NL66462.078.18JapicCTI-194915
• Study Type: interventional
• Target: 103
• Locations: 14 countries
• Sites: 77

Brief Summary

The primary purpose of this study is to determine the efficacy of brigatinib by confirmed objective response rate (ORR) by response evaluation criteria in solid tumors (Response Evaluation Criteria in Solid Tumors \[RECIST\]), in participants with ALK+ locally advanced or metastatic NSCLC whose disease has progressed on therapy with alectinib or ceritinib.

Conditions

ALK-positive Advanced NSCLC

Keywords

Drug Therapy

Outcome Measures

Primary Outcomes (1)

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

  Confirmed ORR is defined as the percentage of the participants who are confirmed to have achieved complete response (CR) or partial response (PR), per RECIST version 1.1 (confirmed ≥4 weeks after initial response), after the initiation of study treatment. CR: disappearance of all extranodal target lesions and all pathological lymph nodes must have decreased to \<10 mm in short axis and PR: at least a 30% decrease in the sum of the longest diameters (SLD) of target lesions taking as reference the Baseline sum diameters. Percentages were rounded off to the nearest single decimal place.

  Up to approximately 20 months from the start of enrollment till data cut-off 30 September 2020

Secondary Outcomes (12)

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

  Up to approximately 28 months

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

  Up to approximately 28 months

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

  Up to approximately 28 Months

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

  Up to approximately 28 months

• Time to Response as Assessed by the IRC and the Investigator

  Up to approximately 28 months

Study Arms (1)

Brigatinib 90 mg/180 mg With Optional Dose Escalation to 240 mg

EXPERIMENTAL

Brigatinib 90 mg, tablets, orally, once daily (QD) for 7 days, followed by brigatinib 180 mg, tablets, orally, QD for until objective disease progression per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, as assessed by the investigator, or intolerable toxicity. Participants who experienced progression on the 180 mg dose and had not experienced toxicities greater than Grade 2 had the option to receive brigatinib 240 mg QD based on investigator's discretion, up to 20 months until data cut-off: 30 September 2020. Participants who experienced progression on any doses but judged as still benefiting from the study treatment by the investigator may continue to use the current dose, up to study end.

Drug: Brigatinib

Interventions

Brigatinib DRUG

Brigatinib Tablets

Also known as: AP26113

Brigatinib 90 mg/180 mg With Optional Dose Escalation to 240 mg

Eligibility Criteria

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

You may qualify if:

• Have histologically or cytologically confirmed stage IIIB (locally advanced or recurrent and not a participant for curative therapy) or stage IV non-small-cell lung cancer (NSCLC).
• Must meet both of the following 2 criteria:
• Have documentation of anaplastic lymphoma kinase (ALK) rearrangement by a positive result from any laboratory test® approved by the food and drug administration (FDA) or Have documented ALK rearrangement by a different test (non-FDA-approved local lab tests) and have provided tumor sample to the central laboratory. (Note: Central laboratory ALK rearrangement testing results are not required to be obtained before randomization.)
• Had been on any one of the ALK tyrosine kinase inhibitor (TKIs) (alectinib, ceritinib, crizotinib) for at least 12 weeks before progression.
• Had progressive disease (PD) while on alectinib or ceritinib
• Had alectinib or ceritinib as the most recent ALK inhibitor therapy.
• Have at least 1 measurable lesion per response evaluation criteria in solid tumors (RECIST) version 1.1 as assessed by the investigator.
• Had recovered from toxicities related to prior anticancer therapy to national cancer institute common terminology criteria for adverse events (NCI CTCAE), version 4.03, Grade \<=1. (Note: Treatment-related alopecia or peripheral neuropathy that are Grade \>1 are allowed if deemed irreversible.) and have adequate major organ functions.
• Have a life expectancy of ≥3 months.

You may not qualify if:

• Had received any prior ALK-targeted TKI other than crizotinib, alectinib, or ceritinib.
• Had received both alectinib and ceritinib.
• Had previously received more than 3 regimens of systemic anticancer therapy for locally advanced or metastatic disease.
• Had symptomatic brain metastasis (parenchymal or leptomeningeal). Participants with asymptomatic brain metastasis or who have stable symptoms that did not require an increased dose of corticosteroids to control symptoms in the past 7 days before the first dose of brigatinib may be enrolled.
• Had current spinal cord compression (symptomatic or asymptomatic and detected by radiographic imaging). Participants with leptomeningeal disease and without cord compression are allowed.
• Had a cerebrovascular accident or transient ischemic attack within 6 months before first dose of brigatinib.
• Had an ongoing or active infection, including, but not limited to, the requirement for intravenous antibiotics.
• Had malabsorption syndrome or other gastrointestinal (GI) illness that could affect oral absorption of brigatinib.

Sponsors & Collaborators

• Ariad Pharmaceuticals: lead
• Takeda: collaborator

Study Sites (80)

University of California Irvine Health Chao Family Comprehensive Cancer Center

Orange, California, 92868, United States

Location

The Oncology Institute of Hope and Innovation

Whittier, California, 90602, United States

Location

USOR - Rocky Mountain Cancer Centers - Pueblo

Pueblo, Colorado, 81008, United States

Location

Florida Hospital Medical Group

Orlando, Florida, 32804, United States

Location

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Levine Cancer Institute - Southpark

Charlotte, North Carolina, 28211, United States

Location

Providence Portland Medical Center

Portland, Oregon, 97213, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

USOR - Virginia Cancer Specialists - Fairfax Office

Fairfax, Virginia, 22031, United States

Location

Saint Vincent's Hospital Melbourne

Fitzroy, Victoria, 3065, Australia

Location

Peninsula & South Eastern Haematology and Oncology Group

Frankston, Victoria, 3199, Australia

Location

Sir Charles Gairdner Hospital

Nedlands, Western Australia, 6009, Australia

Location

Klinikum Klagenfurt Am Worthersee

Klagenfurt, Carinthia, 9020, Austria

Location

Krankenhaus Elisabethinen Linz

Linz, Upper Austria, 4020, Austria

Location

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

Tom Baker Cancer Center

Calgary, British Columbia, T2N 2T9, Canada

Location

Toronto University Health Network

Toronto, Ontario, M5G 2M9, Canada

Location

McGill University Health Centre

Montreal, Quebec, H4A 3J1, Canada

Location

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100000, China

Location

The First Affiliated Hospital of Guangzhou Medical University

Guangzhou, Guangdong, 510000, China

Location

Jilin Provincial Cancer Hospital (Changchun Cancer Hospital)

Changchun, Jilin, 130000, China

Location

Shanghai Pulmonary Hospital

Shanghai, Shanghai Municipality, 200001, China

Location

The First Affiliated Hospital of Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310000, China

Location

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, 310000, China

Location

Hopital Haut-Leveque

Pessac, Aquitaine, 33604, France

Location

Centre de Lutte Contre le Cancer Centre Leon Berard

Lyon, Auvergne-Rhône-Alpes, 69008, France

Location

Hopital Larrey, CHU de Toulouse, Service de Pneumologie

Toulouse, Midi-pyrenees, 31059, France

Location

Assistance Publique-Hopitaux de Marseille Hopital Nord

Marseille, Provence-Alpes-Côte d'Azur Region, 13915, France

Location

Centre Hospitalier Intercommunal de Creteil

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

Location

Thoraxklinik Heidelberg gGmbH

Heidelberg, Baden-Wurttemberg, 69126, Germany

Location

Universitatsklinikum Ulm

Ulm, Baden-Wurttemberg, 89081, Germany

Location

Klinikum Kempten-Oberallgau

Kempten (Allgäu), Bavaria, 87439, Germany

Location

Ludwig-Maximilians-Universitat Munchen

München, Bavaria, 80336, Germany

Location

Pius Hospital Oldenburg

Oldenburg, Lower Saxony, 26121, Germany

Location

Evangelisches Krankenhaus Hamm

Hamm, North Rhine-Westphalia, 59063, Germany

Location

HELIOS Klinikum Emil von Behring

Berlin, 14165, Germany

Location

Prince of Wales Hospital

Shatin, New Territories, Hong Kong

Location

Queen Mary Hospital

Hong Kong, 00852, Hong Kong

Location

Queen Mary Hospital

Hong Kong, Hong Kong

Location

Queen Elizabeth Hospital

Kowloon, 1076, Hong Kong

Location

Princess Margaret Hospital - Hong Kong

Kowloon, Hong Kong

Location

Azienda Ospedaliera San Camillo Forlanini

Rome, Lazio, 00152, Italy

Location

Centro di Riferimento Oncologico di Aviano

Aviano, Pordenone, 33081, Italy

Location

Azienda Ospedaliero - Universitaria San Luigi Gonzaga

Orbassano, Torino, 10043, Italy

Location

Istituto Europeo di Oncologia

Milan, 20141, Italy

Location

Istituto Nazionale Tumori IRCCS Fondazione Pascale

Napoli, 80131, Italy

Location

Azienda Ospedaliero Universitaria di Parma

Parma, 43126, Italy

Location

Azienda USL della Romagna

Ravenna, 48121, Italy

Location

Fujita Health University Hospital

Toyoake, Aichi-ken, 470-1192, Japan

Location

Kanagawa Cancer Center

Yokohama, Kanagawa, 241-8515, Japan

Location

Sendai Kousei Hospital

Sendai, Miyagi, 980-0873, Japan

Location

Okayama University Hospital

Okayama, Okayama-ken, 700-8558, Japan

Location

Kansai Medical University Hirakata Hospital

Hirakata-shi, Osaka, 573-1191, Japan

Location

The Cancer Institute Hospital of Japanese Foundation for Cancer Research

Koto-ku, Tokyo, 135-8550, Japan

Location

Maastricht University Medical Centre

Maastricht, Limburg, 6229 HX, Netherlands

Location

Vrije Universiteit Medisch Centrum

Amsterdam, North Holland, 1081 HV, Netherlands

Location

Erasmus University Medical Center

Rotterdam, South Holland, 3015 CE, Netherlands

Location

National Cancer Center

Goyang-si, Gyeonggi-do, 411-769, South Korea

Location

Gachon University Gil Medical Center

Incheon, Gyeonggi-do, 21565, South Korea

Location

Korea University Anam Hospital

Seoul, Gyeonggi-do, 02841, South Korea

Location

Chungbuk National University Hospital

Cheongju-si, Gyeongsangbuk-do, 28644, South Korea

Location

Keimyung University Dongsan Medical Center

Daegu, 41931, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Severance Hospital

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 135-710, South Korea

Location

Institut Catala d'Oncologia Badalona - Hospital Germans Trias i Pujol

Badalona, Barcelona, 08916, Spain

Location

Complejo Hospitalario Universitario A Coruna

A Coruña, LA Coruna, 15006, Spain

Location

Hospital Universitario Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Universitario Ramon Y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Universitario Puerta de Hierro - Majadahonda

Madrid, 28222, Spain

Location

Skanes Universitetssjukhus i Lund

Lund, Skåne County, 214 01, Sweden

Location

Karolinska Universitetssjukhuset

Stockholm, 171 76, Sweden

Location

Uppsala Akademiska Sjukhus

Uppsala, 751 85, Sweden

Location

Changhua Christian Hospital

Changhua, Changhwa, 500, Taiwan

Location

National Cheng Kung University

Tainan, Tainan CITY, 70403, Taiwan

Location

China Medical University Hospital

Taichung, 404, Taiwan

Location

Taichung Veterans General Hospital

Taichung, 40705, Taiwan

Location

Related Publications (3)

• Mok T, Nishio M, Yoshida T, Ahn MJ, Kudou K, Asato T, Yang H, Tong X, Vincent S, Zhang P, Yamamoto N, Kim ES. Efficacy and safety of brigatinib after alectinib in patients with ALK-positive NSCLC: Integrated analysis of the ALTA-2 and J-ALTA studies. Lung Cancer. 2025 Nov;209:108793. doi: 10.1016/j.lungcan.2025.108793. Epub 2025 Oct 9.

  PMID: 41110382 DERIVED

• Ou SI, Nishio M, Ahn MJ, Mok T, Barlesi F, Zhou C, Felip E, de Marinis F, Kim SW, Perol M, Liu G, Migliorino MR, Kim DW, Novello S, Bearz A, Garrido P, Mazieres J, Morabito A, Lin HM, Yang H, Niu H, Zhang P, Kim ES. Efficacy of Brigatinib in Patients With Advanced ALK-Positive NSCLC Who Progressed on Alectinib or Ceritinib: ALK in Lung Cancer Trial of brigAtinib-2 (ALTA-2). J Thorac Oncol. 2022 Dec;17(12):1404-1414. doi: 10.1016/j.jtho.2022.08.018. Epub 2022 Sep 10.

  PMID: 36096442 DERIVED

• Kim ES, Barlesi F, Mok T, Ahn MJ, Shen J, Zhang P, Ou SI. ALTA-2: Phase II study of brigatinib in patients with ALK-positive, advanced non-small-cell lung cancer who progressed on alectinib or ceritinib. Future Oncol. 2021 May;17(14):1709-1719. doi: 10.2217/fon-2020-1119. Epub 2021 Feb 11.

  PMID: 33569983 DERIVED

MeSH Terms

Interventions

brigatinib

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
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 9, 2018
• First Posted: May 24, 2018
• Study Start: January 31, 2019
• Primary Completion: September 30, 2020
• Study Completion: August 21, 2024
• Last Updated: July 31, 2025
• Results First Posted: October 25, 2021

Record last verified: 2025-07

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

US (10); HK (5); AU (2); FR (5); KR (9); TW (4); IT (7); DE (7); CN (6); NL (3); SE (3); CA (4); ES (6); JP (6)