A Phase 3 Multicenter Open-label Study of Brigatinib (AP26113) Versus Crizotinib in Patients With ALK-positive Advanced Lung Cancer
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 275
- 试验地点
- 91
- 主要终点
- Progression-free Survival (PFS)
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
- •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 (<=)
- •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 <=
- •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.
排除标准
- •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.
- •Have a known or suspected hypersensitivity to brigatinib or its excipients and/or crizotinib or its excipients.
- •Have malabsorption syndrome or other gastrointestinal (GI) illness or condition.
- •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.
研究组 & 干预措施
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).
干预措施: Brigatinib (Drug)
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).
干预措施: Crizotinib (Drug)
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).
干预措施: Brigatinib (Drug)
结局指标
主要结局
Progression-free Survival (PFS)
时间窗: Up to end of study (Up to 56 months)
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.
次要结局
- Disease Control Rate (DCR)(Baseline up to end of treatment (Up to 36 months))
- 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))
- Duration of Response (DOR)(Baseline up to end of study (Up to 56 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))
- Time to Response (TTR)(Baseline up to end of treatment (Up to 36 months))
- Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)(From first dose up to 30 days after last dose of study drug (Up to approximately 37 months))
- Change From Baseline in Global Health Status/Quality of Life as Assessed by EORTC QLQ-C30 (Version 3.0)(Baseline and Month 36)