Clinical trial · Interventional
ALTA-1L Study: A Study of Brigatinib Versus Crizotinib in Anaplastic Lymphoma Kinase Positive (ALK+) Advanced Non-small Cell Lung Cancer (NSCLC) Participants
A Phase 3 Multicenter Open-label Study of Brigatinib (AP26113) Versus Crizotinib in Patients With ALK-positive Advanced Lung Cancer
NCT02737501CI-TRIAL-00053426ALTA-1LcompletedPhase 3Results postedClinicalTrials.gov clinicaltrialsProvenance
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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).
Conditions
Conditions (4)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Advanced Malignancies | — | UNRESOLVED | — |
| Carcinoma | Carcinoma | ONTOLOGY_EXACT | 0.98 |
| Lung Cancer | Malignant Lung Neoplasm | CURATED_EXACT | 0.92 |
| Non-small Cell Lung Cancer | Lung Non-Small Cell Carcinoma | ALIAS | 0.90 |
Interventions
Interventions (2)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Brigatinib | Drug | Brigatinib | ALIAS |
| Crizotinib | Drug | Crizotinib | ALIAS |
Design
Arms and outcomes
Arms (3)
- type
- EXPERIMENTAL
- label
- Randomized Phase: Brigatinib 90 mg QD/180 QD
- description
- 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).
- interventionNames
- Drug: Brigatinib
- type
- ACTIVE_COMPARATOR
- label
- Randomized Phase: Crizotinib 250 mg BID
- description
- 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).
- interventionNames
- Drug: Crizotinib
- type
- EXPERIMENTAL
- label
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
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.
References
Publications (6)
- DERIVEDAl Tawil A, Lauseker M, Mansmann U. Estimating causal effects on quality of life under treatment discontinuation: the ALTA-1L trial. J Clin Epidemiol. 2026 May;193:112189. doi: 10.1016/j.jclinepi.2026.112189. Epub 2026 Feb 23. PMID 41740899
- DERIVEDAhn 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 41410381
- DERIVEDAl 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 39707229
- DERIVEDCamidge 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 32780660
- DERIVEDCamidge 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 30280657
- DERIVEDGainor 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.