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

NCT ID: NCT03535740

Last Updated: 2025-07-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 103 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-01-31
• Study Completion Date: 2024-08-21

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.

Detailed Description

The drug being tested in this study is called brigatinib (AP26113). Brigatinib is being tested to treat people who have anaplastic lymphoma kinase-positive (ALK+), advanced non-small-cell lung cancer (NSCLC).

The study will enroll approximately 103 patients. Participants will be assigned to the treatment group:

• Brigatinib

All participants will be asked to take brigatinib 90 mg tablet in lead-in period for 7 days, followed by brigatinib 180 mg at the same time each day throughout the study. Participants with progressive disease had an option to receive an escalated dose of brigatinib 240 mg as per investigator's discretion in case no toxicities (greater than grade 2) are experienced.

This multicenter trial will be conducted worldwide. The overall time to participate in this study is approximately 3 years. Participants will make multiple visits to the clinic, and 30 days after last dose of study drug for a follow-up assessment.

Conditions

ALK-positive Advanced NSCLC

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

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.

Group Type: EXPERIMENTAL

Brigatinib

Intervention Type: DRUG

Brigatinib Tablets

Interventions

Brigatinib

Brigatinib Tablets

Intervention Type: DRUG

Other Intervention Names

AP26113

Eligibility Criteria

Inclusion Criteria

1. 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).

2. Must meet both of the following 2 criteria:

1. 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.)

2. Had been on any one of the ALK tyrosine kinase inhibitor (TKIs) (alectinib, ceritinib, crizotinib) for at least 12 weeks before progression.

3. Had progressive disease (PD) while on alectinib or ceritinib

4. Had alectinib or ceritinib as the most recent ALK inhibitor therapy.

5. Have at least 1 measurable lesion per response evaluation criteria in solid tumors (RECIST) version 1.1 as assessed by the investigator.

6. 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.

7. Have a life expectancy of ≥3 months.

Exclusion Criteria

1. Had received any prior ALK-targeted TKI other than crizotinib, alectinib, or ceritinib.

2. Had received both alectinib and ceritinib.

3. Had previously received more than 3 regimens of systemic anticancer therapy for locally advanced or metastatic disease.

4. 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.

5. Had current spinal cord compression (symptomatic or asymptomatic and detected by radiographic imaging). Participants with leptomeningeal disease and without cord compression are allowed.

6. Had a cerebrovascular accident or transient ischemic attack within 6 months before first dose of brigatinib.

7. Had an ongoing or active infection, including, but not limited to, the requirement for intravenous antibiotics.

8. Had malabsorption syndrome or other gastrointestinal (GI) illness that could affect oral absorption of brigatinib.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Takeda

INDUSTRY

Sponsor Role: collaborator

Ariad Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Takeda

Locations

University of California Irvine Health Chao Family Comprehensive Cancer Center

Orange, California, United States

The Oncology Institute of Hope and Innovation

Whittier, California, United States

USOR - Rocky Mountain Cancer Centers - Pueblo

Pueblo, Colorado, United States

Florida Hospital Medical Group

Orlando, Florida, United States

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

Washington University School of Medicine

St Louis, Missouri, United States

Levine Cancer Institute - Southpark

Charlotte, North Carolina, United States

Providence Portland Medical Center

Portland, Oregon, United States

Sarah Cannon Research Institute

Nashville, Tennessee, United States

USOR - Virginia Cancer Specialists - Fairfax Office

Fairfax, Virginia, United States

Saint Vincent's Hospital Melbourne

Fitzroy, Victoria, Australia

Peninsula & South Eastern Haematology and Oncology Group

Frankston, Victoria, Australia

Sir Charles Gairdner Hospital

Nedlands, Western Australia, Australia

Klinikum Klagenfurt Am Worthersee

Klagenfurt, Carinthia, Austria

Krankenhaus Elisabethinen Linz

Linz, Upper Austria, Austria

Cross Cancer Institute

Edmonton, Alberta, Canada

Tom Baker Cancer Center

Calgary, British Columbia, Canada

Toronto University Health Network

Toronto, Ontario, Canada

McGill University Health Centre

Montreal, Quebec, Canada

Beijing Cancer Hospital

Beijing, Beijing Municipality, China

The First Affiliated Hospital of Guangzhou Medical University

Guangzhou, Guangdong, China

Jilin Provincial Cancer Hospital (Changchun Cancer Hospital)

Changchun, Jilin, China

Shanghai Pulmonary Hospital

Shanghai, Shanghai Municipality, China

The First Affiliated Hospital of Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, China

Hopital Haut-Leveque

Pessac, Aquitaine, France

Centre de Lutte Contre le Cancer Centre Leon Berard

Lyon, Auvergne-Rhône-Alpes, France

Hopital Larrey, CHU de Toulouse, Service de Pneumologie

Toulouse, Midi-pyrenees, France

Assistance Publique-Hopitaux de Marseille Hopital Nord

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

Centre Hospitalier Intercommunal de Creteil

Créteil, Île-de-France Region, France

Thoraxklinik Heidelberg gGmbH

Heidelberg, Baden-Wurttemberg, Germany

Universitatsklinikum Ulm

Ulm, Baden-Wurttemberg, Germany

Klinikum Kempten-Oberallgau

Kempten (Allgäu), Bavaria, Germany

Ludwig-Maximilians-Universitat Munchen

München, Bavaria, Germany

Pius Hospital Oldenburg

Oldenburg, Lower Saxony, Germany

Evangelisches Krankenhaus Hamm

Hamm, North Rhine-Westphalia, Germany

HELIOS Klinikum Emil von Behring

Berlin, , Germany

Prince of Wales Hospital

Shatin, New Territories, Hong Kong

Queen Mary Hospital

Hong Kong, , Hong Kong

Queen Mary Hospital

Hong Kong, , Hong Kong

Queen Elizabeth Hospital

Kowloon, , Hong Kong

Princess Margaret Hospital - Hong Kong

Kowloon, , Hong Kong

Azienda Ospedaliera San Camillo Forlanini

Rome, Lazio, Italy

Centro di Riferimento Oncologico di Aviano

Aviano, Pordenone, Italy

Azienda Ospedaliero - Universitaria San Luigi Gonzaga

Orbassano, Torino, Italy

Istituto Europeo di Oncologia

Milan, , Italy

Istituto Nazionale Tumori IRCCS Fondazione Pascale

Napoli, , Italy

Azienda Ospedaliero Universitaria di Parma

Parma, , Italy

Azienda USL della Romagna

Ravenna, , Italy

Fujita Health University Hospital

Toyoake, Aichi-ken, Japan

Kanagawa Cancer Center

Yokohama, Kanagawa, Japan

Sendai Kousei Hospital

Sendai, Miyagi, Japan

Okayama University Hospital

Okayama, Okayama-ken, Japan

Kansai Medical University Hirakata Hospital

Hirakata-shi, Osaka, Japan

The Cancer Institute Hospital of Japanese Foundation for Cancer Research

Koto-ku, Tokyo, Japan

Maastricht University Medical Centre

Maastricht, Limburg, Netherlands

Vrije Universiteit Medisch Centrum

Amsterdam, North Holland, Netherlands

Erasmus University Medical Center

Rotterdam, South Holland, Netherlands

National Cancer Center

Goyang-si, Gyeonggi-do, South Korea

Gachon University Gil Medical Center

Incheon, Gyeonggi-do, South Korea

Korea University Anam Hospital

Seoul, Gyeonggi-do, South Korea

Chungbuk National University Hospital

Cheongju-si, Gyeongsangbuk-do, South Korea

Keimyung University Dongsan Medical Center

Daegu, , South Korea

Seoul National University Hospital

Seoul, , South Korea

Severance Hospital

Seoul, , South Korea

Asan Medical Center

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

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

Badalona, Barcelona, Spain

Complejo Hospitalario Universitario A Coruna

A Coruña, LA Coruna, Spain

Hospital Universitario Vall d'Hebron

Barcelona, , Spain

Hospital Universitario Ramon Y Cajal

Madrid, , Spain

Hospital Universitario La Paz

Madrid, , Spain

Hospital Universitario Puerta de Hierro - Majadahonda

Madrid, , Spain

Skanes Universitetssjukhus i Lund

Lund, Skåne County, Sweden

Karolinska Universitetssjukhuset

Stockholm, , Sweden

Uppsala Akademiska Sjukhus

Uppsala, , Sweden

Changhua Christian Hospital

Changhua, Changhwa, Taiwan

National Cheng Kung University

Tainan City, Tainan CITY, Taiwan

China Medical University Hospital

Taichung, , Taiwan

Taichung Veterans General Hospital

Taichung, , Taiwan

Countries

United States; Australia; Austria; Canada; China; France; Germany; Hong Kong; Italy; Japan; Netherlands; South Korea; Spain; Sweden; Taiwan

References

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 Oct 9;209:108793. doi: 10.1016/j.lungcan.2025.108793. Online ahead of print.

Reference Type: DERIVED

PMID: 41110382 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 36096442 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33569983 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2018-000635-27

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

NL66462.078.18

Identifier Type: REGISTRY

Identifier Source: secondary_id

JapicCTI-194915

Identifier Type: REGISTRY

Identifier Source: secondary_id

Brigatinib-2002

Identifier Type: -

Identifier Source: org_study_id