ALTA-1L Study: A Study of Brigatinib Versus Crizotinib in Anaplastic Lymphoma Kinase Positive (ALK+) Advanced Non-small Cell Lung Cancer (NSCLC) Participants
ALTA-1L
A Phase 3 Multicenter Open-label Study of Brigatinib (AP26113) Versus Crizotinib in Patients With ALK-positive Advanced Lung Cancer
3 other identifiers
interventional
275
18 countries
89
Brief Summary
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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_3 nonsmall-cell-lung-cancer
Started May 2016
89 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 30, 2016
CompletedFirst Posted
Study publicly available on registry
April 14, 2016
CompletedStudy Start
First participant enrolled
May 26, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 28, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
January 29, 2021
CompletedResults Posted
Study results publicly available
August 20, 2021
CompletedAugust 20, 2021
July 1, 2021
4.2 years
March 30, 2016
July 27, 2021
July 27, 2021
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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)
Secondary Outcomes (9)
Confirmed Objective Response Rate (ORR)
Baseline up to end of treatment (Up to 36 months)
Confirmed Intracranial ORR (iORR)
Baseline up to end of treatment (Up to 36 months)
Intracranial Progression Free Survival
Baseline up to end of study (Up to 56 months)
Overall Survival (OS)
Baseline up to end of study (Up to 56 months)
Duration of Response (DOR)
Baseline up to end of study (Up to 56 months)
- +4 more secondary outcomes
Study Arms (3)
Randomized Phase: Brigatinib 90 mg QD/180 QD
EXPERIMENTALBrigatinib 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 COMPARATORCrizotinib 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
EXPERIMENTALParticipants 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).
Interventions
Brigatinib tablets
Eligibility Criteria
You may qualify if:
- Have histologically or cytologically confirmed stage IIIB (and not a candidate for definitive multimodality therapy) or stage four (IV) NSCLC.
- Must have documented ALK rearrangement.
- Have sufficient tumor tissue available for central analysis.
- Have at least 1 measurable (that is, target) lesion per RECIST v1.1.
- Recovered from toxicities related to prior anticancer therapy to National Cancer Institute (of the United States) (NCI) Common Terminology Criteria for Adverse Events (version 4.0) (CTCAE v 4.0) grade be less than or equal to (\<=) 1.
- Are a male or female participants greater than or equal to (\>=)18 years old.
- Have adequate organ function, as defined by the study protocol.
- Have Eastern Cooperative Oncology Group (ECOG) performance status \<=2.
- Have normal QT interval on screening ECG evaluation, defined as QT interval corrected (Fridericia) (QTcF) of \<= 450 millisecond (msec) in males or \<=470 msec in females.
- For female participants of childbearing potential, have a negative pregnancy test documented prior to randomization.
- For female and male participants who are fertile, agree to use a highly effective form of contraception, as defined by the study protocol.
- Provide signed and dated informed consent indicating that the participants has been informed of all pertinent aspects of the study, including the potential risks, and is willingly participating.
- Have the willingness and ability to comply with scheduled visit and study procedures.
You may not qualify if:
- Previously received an investigational antineoplastic agent for NSCLC.
- Previously received any prior tyrosine kinase inhibitor (TKI), including ALK-targeted TKIs.
- Previously received more than 1 regimen of systemic anticancer therapy for locally advanced or metastatic disease.
- Received chemotherapy or radiation within 14 days of first dose of study drug, except stereotactic radiosurgery (SRS) or stereotactic body radiation therapy (SBRT).
- Received anti-neoplastic monoclonal antibodies within 30 days of the first dose of study drug.
- Had major surgery within 30 days of the first dose of study drug, minor surgical procedures such as catheter placement or minimally invasive biopsies are allowed.
- Have been diagnosed with another primary malignancy other than NSCLC, except for adequately treated non-melanoma skin cancer or cervical cancer in situ; definitively treated non-metastatic 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.
- Have symptomatic CNS metastases (parenchymal or leptomeningeal) at screening or asymptomatic disease requiring an increasing dose of corticosteroids to control symptoms within 7 days prior to randomization.
- Have current spinal cord compression (symptomatic or asymptomatic and detected by radiographic imaging). Participants with leptomeningeal disease and without cord compression are allowed.
- Be pregnant, planning a pregnancy, or breastfeeding.
- Have significant, uncontrolled, or active cardiovascular disease, as defined by the study protocol.
- Have uncontrolled hypertension.
- Have a history or the presence at baseline of pulmonary interstitial disease, drug-related pneumonitis, or radiation pneumonitis.
- Have an ongoing or active infection.
- Have a known history of human immunodeficiency virus (HIV) infection.
- +3 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (91)
USOR - Arizona Oncology Associates - Sedona
Sedona, Arizona, 86336, United States
Kaiser Permanente Bellflower Medical Offices
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, ÃŽle-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
Napoli, 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
Related Publications (5)
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.
PMID: 41410381DERIVEDAl 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.
PMID: 39707229DERIVEDCamidge 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.
PMID: 32780660DERIVEDCamidge 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.
PMID: 30280657DERIVEDGainor 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.
PMID: 28501139DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Study Director
- Organization
- Takeda
Study Officials
- STUDY DIRECTOR
Medical Director
Takeda
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- 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
March 30, 2016
First Posted
April 14, 2016
Study Start
May 26, 2016
Primary Completion
July 28, 2020
Study Completion
January 29, 2021
Last Updated
August 20, 2021
Results First Posted
August 20, 2021
Record last verified: 2021-07
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.
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.