A Phase III, Randomized, Double-blind Study to Assess the Efficacy and Safety of Lazertinib Versus Gefitinib as the First-line Treatment in Patients With Epidermal Growth Factor Receptor Sensitizing Mutation Positive, Locally Advanced or Metastatic Non-Small Cell Lung Cancer
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 393
- 试验地点
- 138
- 主要终点
- Progression-Free Survival (PFS) According to RECIST v1.1 by Investigator Assessment
研究概览
简要总结
This Phase III study will be conducted to evaluate the efficacy and safety of YH25448 as first-line treatment in locally advanced or metastatic Non-small Cell Lung Cancer (NSCLC) patients with EGFR mutations
详细描述
YH25448 is an oral, highly potent, mutant-selective and irreversible EGFR Tyrosine-kinase inhibitors (TKIs) that targets both the T790M mutation and activating EGFR mutations while sparing wild type EGFR.
This is a Phase III, Randomized, Double-blind study evaluating the efficacy and safety of YH25448 (240 mg orally, once daily) versus Gefitinib (250 mg orally, once daily) in patients with locally advanced or metastatic NSCLC that is known to be EGFR sensitizing mutation (EGFRm) positive, treatment-naïve and eligible for first-line treatment with an EGFR-TKI.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Pathologically confirmed adenocarcinoma of the lung
- •Locally advanced or metastatic NSCLC, not amenable to curative surgery or radiotherapy
- •At least 1 of the 2 common EGFR mutations known to be associated with EGFR TKI sensitivity (Ex19del or L858R), either alone or in combination with other EGFR mutations
- •Treatment-naïve for locally advanced or metastatic NSCLC
- •WHO performance status score of 0 to 1 with no clinically significant deterioration over the previous 2 weeks before randomization
- •At least 1 measurable lesion, not previously irradiated and not chosen for biopsy during the study Screening period
排除标准
- •Symptomatic and unstable brain metastases
- •Leptomeningeal metastases
- •Symptomatic spinal cord compression
- •History of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD
- •Any medical conditions requiring chronic continuous oxygen therapy
- •History of any malignancy other than the disease under study within 3 years before randomization
- •Any cardiovascular disease as follows:
- •History of symptomatic chronic heart failure or serious cardiac arrhythmia requiring active treatment
- •History of myocardial infarction or unstable angina within 24 weeks of randomization
研究组 & 干预措施
Lazertinib + Gefitinib-matching placebo
Lazertinib (240 mg or 160 mg orally, once daily) plus Gefitinib-matching placebo (250 mg orally, once daily) in accordance with the randomization schedule
干预措施: Gefitinib-matching placebo 250 mg (Drug)
Gefitinib + Lazertinib-matching placebo
Gefitinib (250 mg orally, once daily) plus Lazertinib-matching placebo (240 mg or 160 mg orally, once daily) in accordance with the randomization schedule
干预措施: Gefitinib 250 mg (Drug)
Lazertinib + Gefitinib-matching placebo
Lazertinib (240 mg or 160 mg orally, once daily) plus Gefitinib-matching placebo (250 mg orally, once daily) in accordance with the randomization schedule
干预措施: Lazertinib 240 mg/160 mg (Drug)
Gefitinib + Lazertinib-matching placebo
Gefitinib (250 mg orally, once daily) plus Lazertinib-matching placebo (240 mg or 160 mg orally, once daily) in accordance with the randomization schedule
干预措施: Lazertinib-matching placebo 240 mg/160 mg (Drug)
结局指标
主要结局
Progression-Free Survival (PFS) According to RECIST v1.1 by Investigator Assessment
时间窗: At baseline and every 6 weeks for the first 18 months and then every 12 weeks relative to randomization until progression, assessed up to 29 months per participant.
PFS was defined as the time from randomization until the date of objective progression or death(by any cause whichever comes first based on investigator assessment using RECIST v1.1 and was used to assess the efficacy of lazertinib compared to the gefitinib).
次要结局
- Disease Control Rate (DCR) According to RECIST v1.1 by Investigator Assessments(At baseline and every 6 weeks for the first 18 months and then every 12 weeks relative to randomization until progression, assessed up to 29 months per participant.)
- Change From Baseline in Euro-Quality of Life-5 Dimension-5 Level (EQ-5D-5L)(Questionnaires completed at Cycle 1 Day1 , Cycle2 Day 1 and then every 6 weeks relative to the randomization date until 28d safety f/u or progression f/u visit(whichever is later).)
- Time to Response According to RECIST v1.1 by Investigator Assessments(At baseline and every 6 weeks for the first 18 months and then every 12 weeks relative to randomization until progression.)
- Cerebrospinal Fluid (CSF) Concentrations of Lazertinib(A cerebrospinal fluid (CSF) sample once collected from participants with brain metastases, at Cycle 5 Day 1 or afterward.)
- Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 Items (QLQ-C30)(Questionnaires completed at Cycle 1 Day1 , Cycle2 Day 1 and then every 6 weeks relative to the randomization date until 28d safety f/u or progression f/u visit(whichever is later).)
- Depth of Response According to RECIST v1.1 by Investigator Assessments(At baseline and every 6 weeks for the first 18 months and then every 12 weeks relative to randomization until progression.)
- Overall Survival (OS)(From the randomization to end of study or date of death from any cause, whichever comes first, assessed every 6 weeks. (Up to 29 months per participant.))
- Objective Response Rate (ORR) According to RECIST v1.1 by Investigator Assessments(At baseline and every 6 weeks for the first 18 months and then every 12 weeks relative to randomization until progression, assessed up to 29 months per participant.)
- Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaires Lung Cancer 13 Items (EORTC QLQ-LC13)(Questionnaires completed at Cycle 1 Day1 , Cycle2 Day 1 and then every 6 weeks relative to the randomization date until 28d safety f/u or progression f/u visit(whichever is later).)
- Duration of Response (DoR) According to RECIST v1.1 by Investigator Assessments(At baseline and every 6 weeks for the first 18 months and then every 12 weeks relative to randomization until progression, assessed up to 29 months per participant.)
- Plasma Concentrations of Lazertinib(Blood samples collected from each participant at pre-dose, 1 to 3 hours, and 4 to 6 hours post-dose on Day 1 Cycle 1, Day 1 Cycle 2, Day 1 Cycle 5, Day 1 Cycle 9, and Day 1 Cycle 13.)