ALTA-1L Study: A Study of Brigatinib Versus Crizotinib in Anaplastic Lymphoma Kinase Positive (ALK+) Advanced Non-small Cell Lung Cancer (NSCLC) Participants

NCT ID: NCT02737501

Last Updated: 2021-08-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 275 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-05-26
• Study Completion Date: 2021-01-29

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).

Detailed Description

The purpose of this phase III, randomized, open-label, comparative, multicenter, international study is to compare the efficacy and safety of brigatinib to that of crizotinib in ALK+ locally advanced or metastatic NSCLC participants who have not previously been treated with an ALK inhibitor. Participants will be stratified by the presence of CNS metastases at baseline and prior chemotherapy used for locally advanced or metastatic disease. Participants will be randomized in a 1:1 ratio to receive either brigatinib, 90 mg orally once daily (QD) for 7 days, then a 180 mg orally QD, or crizotinib, 250 mg orally twice daily (BID). Participants will receive treatment until disease progression, intolerable toxicity, consent withdrawal, or death. Crossover from crizotinib to brigatinib is also permitted.

The total estimated duration of the study is at least 4.5 years, including 1.5 years to accrue participants, with at least 3 years for treatment and follow-up.

Conditions

Non-small Cell Lung Cancer; Lung Cancer; Advanced Malignancies; Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Randomized Phase: Brigatinib 90 mg QD/180 QD

Brigatinib 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).

Group Type: EXPERIMENTAL

Brigatinib

Intervention Type: DRUG

Brigatinib tablets

Randomized Phase: Crizotinib 250 mg BID

Crizotinib 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).

Group Type: ACTIVE_COMPARATOR

Crizotinib

Intervention Type: DRUG

Crizotinib tablets

Crossover Phase: Brigatinib 90 mg QD/180 mg QD

Participants 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).

Group Type: EXPERIMENTAL

Brigatinib

Intervention Type: DRUG

Brigatinib tablets

Interventions

Brigatinib

Brigatinib tablets

Intervention Type: DRUG

Crizotinib

Crizotinib tablets

Intervention Type: DRUG

Other Intervention Names

Xalkori

Eligibility Criteria

Inclusion Criteria

1. Have histologically or cytologically confirmed stage IIIB (and not a candidate for definitive multimodality therapy) or stage four (IV) NSCLC.

2. Must have documented ALK rearrangement.

3. Have sufficient tumor tissue available for central analysis.

4. Have at least 1 measurable (that is, target) lesion per RECIST v1.1.

5. 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.

6. Are a male or female participants greater than or equal to (>=)18 years old.

7. Have adequate organ function, as defined by the study protocol.

8. Have Eastern Cooperative Oncology Group (ECOG) performance status <=2.

9. 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.

10. For female participants of childbearing potential, have a negative pregnancy test documented prior to randomization.

11. For female and male participants who are fertile, agree to use a highly effective form of contraception, as defined by the study protocol.

12. 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.

13. Have the willingness and ability to comply with scheduled visit and study procedures.

Exclusion Criteria

1. Previously received an investigational antineoplastic agent for NSCLC.

2. Previously received any prior tyrosine kinase inhibitor (TKI), including ALK-targeted TKIs.

3. Previously received more than 1 regimen of systemic anticancer therapy for locally advanced or metastatic disease.

4. Received chemotherapy or radiation within 14 days of first dose of study drug, except stereotactic radiosurgery (SRS) or stereotactic body radiation therapy (SBRT).

5. Received anti-neoplastic monoclonal antibodies within 30 days of the first dose of study drug.

6. 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.

7. 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.

8. 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.

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

10. Be pregnant, planning a pregnancy, or breastfeeding.

11. Have significant, uncontrolled, or active cardiovascular disease, as defined by the study protocol.

12. Have uncontrolled hypertension.

13. Have a history or the presence at baseline of pulmonary interstitial disease, drug-related pneumonitis, or radiation pneumonitis.

14. Have an ongoing or active infection.

15. Have a known history of human immunodeficiency virus (HIV) infection.

16. Have a known or suspected hypersensitivity to brigatinib or its excipients and/or crizotinib or its excipients.

17. Have malabsorption syndrome or other gastrointestinal (GI) illness or condition.

18. Have any condition or illness that, in the opinion of the investigator, would compromise participant's safety or interfere with the evaluation of the study drug.

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

Sponsors

Ariad Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Takeda

Locations

USOR - Arizona Oncology Associates - Sedona

Sedona, Arizona, United States

Kaiser Permanente Bellflower Medical Offices

Bellflower, California, United States

University of Colorado Cancer Center

Aurora, Colorado, United States

Rocky Mountain Cancer Centers - Boulder

Boulder, Colorado, United States

Sylvester Comprehensive Cancer Center

Deerfield Beach, Florida, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

West Michigan Cancer Center

Kalamazoo, Michigan, United States

Minnesota Oncology

Coon Rapids, Minnesota, United States

Montefiore Medical Center

The Bronx, New York, United States

Oncology Hematology Care - Blue Ash

Cincinnati, Ohio, United States

Stephenson Cancer Center

Oklahoma City, Oklahoma, United States

Virginia Cancer Specialists - Fairfax Office

Fairfax, Virginia, United States

Saint George Hospital

Kogarah, New South Wales, Australia

Royal North Shore Hospital

St Leonards, New South Wales, Australia

Monash Medical Centre

Bentleigh East, Victoria, Australia

Saint Vincent's Hospital Melbourne

Fitzroy, Victoria, Australia

Universitatsklinium St. Polten

Sankt Pölten, Lower Austria, Austria

Otto-Wagner-Spital Baumgartner Hohe

Vienna, , Austria

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Odense University Hospital

Odense C, , Denmark

Hopital Albert Michallon

Grenoble, Auvergne-Rhône-Alpes, France

Centre Leon Berard

Lyon, Auvergne-Rhône-Alpes, France

Centre de Lutte Contre le Cancer Francois Baclesse

Caen, Basse-normandie, France

Hopital Charles Nicolle

Rouen, Haute-normandie, France

Centre Hospitalier Universitaire Hopital Nord

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

Centre Hospitalier Intercommunal de Creteil

Créteil, Île-de-France Region, France

Hopital Tenon

Paris, Île-de-France Region, France

Universitatsklinik Freiburg

Freiburg im Breisgau, Baden-Wurttemberg, Germany

Thoraxklinik Heidelberg gGmbH

Heidelberg, Baden-Wurttemberg, Germany

Pius Hospital Oldenburg

Oldenburg, Lower Saxony, Germany

Kliniken der Stadt Koeln gGmbH - Krankenhaus Merheim

Cologne, North Rhine-Westphalia, Germany

Evangelische Lungenklinik Berlin

Berlin, , Germany

Studiengesellschaft Haemato-Onkologie Hamburg Prof. Laack und Partner

Hamburg, , Germany

Tuen Mun Hospital

Tuenmen, New Territories, Hong Kong

Queen Mary Hospital

Hong Kong, , Hong Kong

Queen Elizabeth Hospital

Kowloon, , Hong Kong

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori

Meldola, Forli-cesena, Italy

Azienda Ospedaliera San Gerardo di Monza

Monza, Monza E Brianza, Italy

Centro di Riferimento Oncologico di Aviano

Aviano, Pordenone, Italy

Azienda Ospedaliera San Giuseppe Moscati

Avellino, , Italy

Istituto Oncologico di Bari Giovanni Paolo II

Bari, , Italy

Azienda Ospedaliero Universitaria di Bologna Policlinico Sant'Orsola-Malpighi

Bologna, , Italy

Istituto Scientifico Universitario San Raffaele

Milan, , Italy

Istituto Europeo di Oncologia

Milan, , Italy

Istituto Tumori Napoli Fondazione G. Pascale

Napoli, , Italy

Azienda Ospedaliero Universitaria Maggiore della Carita

Novara, , Italy

Azienda Ospedaliera di Perugia - Ospedale S. Maria della Misericordia

Perugia, , Italy

Azienda Unita Sanitaria Locale di Ravenna

Ravenna, , Italy

Policlinico Universitario Campus Bio-Medico

Roma, , Italy

Centre Hospitalier de Luxembourg - Hopital Municipal

Luxembourg, , Luxembourg

Amphia Ziekenhuis - Locatie Langendijk Breda

Breda, North Brabant, Netherlands

Antoni van Leeuwenhoekziekenhuis

Amsterdam, North Holland, Netherlands

Isala Klinieken

Zwolle, Overijssel, Netherlands

Universitair Medisch Centrum Groningen

Groningen, , Netherlands

Radiumhospitalet

Oslo, , Norway

National University Hospital

Singapore, , Singapore

National Cancer Centre Singapore

Singapore, , Singapore

OncoCare Cancer Centre

Singapore, , Singapore

National Cancer Center

Goyang-si, Gyeonggi-do, South Korea

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, South Korea

Chungbuk National University Hospital

Cheongju-si, North Chungcheong, 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

The Catholic University of Korea

Seoul, , South Korea

Hospital Universitari Germans Trias i Pujol

Badalona, Barcelona, Spain

Hospital Universitario Puerta de Hierro - Majadahonda

Majadahonda, Madrid, Spain

Hospital Universitario Central de Asturias

Oviedo, Principality of Asturias, Spain

Hospital Teresa Herrera - Materno Infantil

A Coruña, , Spain

Hospital General Universitario de Alicante

Alicante, , Spain

Hospital Universitario Vall d'Hebron

Barcelona, , Spain

Hospital Ramon Y Cajal

Madrid, , Spain

Hospital Universitario La Paz

Madrid, , Spain

Hospital Regional Universitario Carlos Haya Malaga Instituto de Neurociencias Clinicas

Málaga, , Spain

Hospital Universitario Marques de Valdecilla

Santander, , Spain

Hospital Universitario Virgen del Rocio

Seville, , Spain

Hospital Clinico Universitario de Valencia

Valencia, , Spain

Karolinska Universitetssjukhuset

Stockholm, , Sweden

University Hospital Zurich

Zurich, , Switzerland

National Cheng Kung University

Tainan, Taipei, Taiwan

China Medical University Hospital

Taichung, , Taiwan

Taichung Veterans General Hospital

Taichung, , Taiwan

National Taiwan University Hospital

Taipei, , Taiwan

Taipei Veterans General Hospital

Taipei, , Taiwan

Leicester Royal Infirmary

Leicester, England, United Kingdom

University College London

London, England, United Kingdom

Guy's and Saint Thomas' NHS Foundation Trust

London, England, United Kingdom

Royal Marsden NHS Trust

London, England, United Kingdom

Maidstone Hospital

Maidstone, England, United Kingdom

The Christie NHS Foundation Trust

Manchester, England, United Kingdom

Countries

United States; Australia; Austria; Canada; Denmark; France; Germany; Hong Kong; Italy; Luxembourg; Netherlands; Norway; Singapore; South Korea; Spain; Sweden; Switzerland; Taiwan; United Kingdom

References

Al 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.

Reference Type: DERIVED

PMID: 39707229 (View on PubMed)

Camidge 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.

Reference Type: DERIVED

PMID: 32780660 (View on PubMed)

Camidge 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.

Reference Type: DERIVED

PMID: 30280657 (View on PubMed)

Gainor 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.

Reference Type: DERIVED

PMID: 28501139 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

U1111-1210-4363

Identifier Type: OTHER

Identifier Source: secondary_id

2015-003447-19

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

AP26113-13-301

Identifier Type: -

Identifier Source: org_study_id