ALTA-1L Study: A Phase 3 Study of Brigatinib Versus Crizotinib in Anaplastic Lymphoma Kinase Positive (ALK+) Advanced Non-small Cell Lung Cancer (NSCLC) Participants

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02737501
• Date of registration: 30/03/2016
• Prospective Registration: Yes
• Primary sponsor: Ariad Pharmaceuticals
• Public title: ALTA-1L Study: A Phase 3 Study of Brigatinib Versus Crizotinib in Anaplastic Lymphoma Kinase Positive (ALK+) Advanced Non-small Cell Lung Cancer (NSCLC) Participants ALTA-1L
• Scientific title: A Phase 3 Multicenter Open-label Study of Brigatinib (AP26113) Versus Crizotinib in Patients With ALK-positive Advanced Lung Cancer
• Date of first enrolment: May 26, 2016
• Target sample size: 275
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/show/NCT02737501
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

Australia, Austria, Canada, Denmark, Finland, France, Germany, Hong Kong, Italy, Korea, Republic of, Luxembourg, Netherlands, Norway, Singapore, Spain, Sweden, Switzerland, Taiwan, United Kingdom, United States

Contacts

• Name: Medical Director
• Affiliation: Takeda

Key inclusion & exclusion 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.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Advanced Malignancies

Non-small Cell Lung Cancer

Carcinoma

Lung Cancer

Intervention(s)

Drug: Brigatinib

Drug: Crizotinib

Primary Outcome(s)

Progression-free Survival (PFS) [Time Frame: Baseline up to approximately 36 months]

Secondary Outcome(s)

Disease Control Rate (DCR) [Time Frame: Baseline up to approximately 36 months]

Intracranial ORR [Time Frame: Baseline up to approximately 36 months]

Intracranial PFS [Time Frame: Baseline up to approximately 36 months]

Percentage of Participants with Adverse Events [Time Frame: Baseline until 30 days after the last dose of study treatment (approximately 3 years)]

Objective Response Rate (ORR) [Time Frame: Baseline up to approximately 36 months]

Overall Survival (OS) [Time Frame: Baseline up to approximately 36 months]

Time to Response (TTR) [Time Frame: Baseline up to approximately 36 months]

Health-related Quality of Life (HRQoL) [Time Frame: Baseline until 30 days after the last dose of study treatment (approximately 3 years)]

Duration of Response [Time Frame: Baseline up to approximately 36 months]

Secondary ID(s)

U1111-1210-4363

AP26113-13-301

2015-003447-19

Source(s) of Monetary Support

Please refer to primary and secondary sponsors