MELROSE: Phase 2 Study Evaluating MEchanisms of Resistance on Tumor Tissue and Liquid Biopsy in Patients With EGFR Mutated Nonpretreated Advanced Lung Cancer Receiving OSimErtinib Until and Beyond Radiological Progression : the MELROSE Trial
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 150
- 试验地点
- 17
- 主要终点
- Examination of the genetic profile at the point of disease progression in EGFRm+ (mutated Epidermal Growth Factor Receptor) patients receiving osimertinib as first-line EGFR TKI therapy compared to baseline.
研究概览
简要总结
Osimertinib is an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that is selective for both EGFR-TKI sensitizing and T790M resistance mutations in patients with non-small-cell lung cancer.
The AURA 3 study (T790M-positive advanced non-small-cell lung cancer in progression after first-line EGFR-TKI therapy, shown that the median duration of progression-free survival was significantly longer with osimertinib than with platinum therapy plus pemetrexed (10.1 months vs. 4.4 months p<0.001).
In addition, clinical data show that patients with mutated EGFR NSCLC receiving osimertinib in first line, presented an objective response rate of 77 % with a disease control rate of 98 % and a median PFS was 19.3 months.
Finally, The FLAURA study randomized phase 3 study clearly demonstrated the superiority of osimertinib compared with erlotinib or gefitinib in EGFR mutated nonpretreated NSCLC (median PFS of 18.9 months versus 10.2 months).
However, several issues remain unknown or debated :
- What are the mechanisms of resistance to osimertinib prescribed in first-line?
- What are the consequences of prolonged exposure to osimertinib on the expression of markers of response to immunotherapy?
- Is there an association between kinetic parameters of ctDNA (circulating tumor DNA) and prediction of response to osimertinib and/ or and prediction of therapeutic escape under osimertinib? In order to respond to all these questions, this phase II trial will be the first to systemically analyze the mechanisms of resistance to Osimertinib based on the analysis of biopsy, and collection of plasma from all patients during the course of treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
TAGRISSO® 80mg (Osimertinib)
Oral administration of TAGRISSO® 80mg (Osimertinib) as a single daily dose until disease progression or unacceptable toxicity.
Tumor biopsies performed at baseline and clinical progression. ctDNA analysis by Collection of plasma (two 10-ml Streck tubes) at each time point indicated in the trial.
干预措施: TAGRISSO® 80mg (Osimertinib) (Drug)
TAGRISSO® 80mg (Osimertinib)
Oral administration of TAGRISSO® 80mg (Osimertinib) as a single daily dose until disease progression or unacceptable toxicity.
Tumor biopsies performed at baseline and clinical progression. ctDNA analysis by Collection of plasma (two 10-ml Streck tubes) at each time point indicated in the trial.
干预措施: Tumor biopsies (Genetic)
TAGRISSO® 80mg (Osimertinib)
Oral administration of TAGRISSO® 80mg (Osimertinib) as a single daily dose until disease progression or unacceptable toxicity.
Tumor biopsies performed at baseline and clinical progression. ctDNA analysis by Collection of plasma (two 10-ml Streck tubes) at each time point indicated in the trial.
干预措施: ctDNA analysis (Genetic)
结局指标
主要结局
Examination of the genetic profile at the point of disease progression in EGFRm+ (mutated Epidermal Growth Factor Receptor) patients receiving osimertinib as first-line EGFR TKI therapy compared to baseline.
时间窗: At clinical disease progression (approximately 22 months)
Analyze of the proportion of patients with a given genetic marker on tumor biopsy (including, but not limited to, EGFR mutations, HER2 (Human Epidermal Growth factor receptor 2), and cMET expression and/or amplification) at the point of clinical disease progression.
次要结局
- Clinical objective : To assess efficacy of Osimertinib(every 3 months until radiological disease progression (approximately 22 months))
- Clinical objective : To assess efficacy of Osimertinib: Duration of Response (DoR): Disease Control Rate (DCR)(every 3 months until radiological disease progression (approximately 22 months))
- Clinical objective : To assess safety of Osimertinib with Monitoring of Adverse events (grade 3 and 4)(monthly from first study dose until 15 days after last study dose)
- Biological objective : To evaluate diagnostic accuracy of ctDNA to detect mutation(At baseline and monthly until clinical disease progression (approximately 22 months))
- Biological objective : To compare the genetic profile of the ctDNA and the tumor biopsy(At baseline and at clinical disease progression (approximately 22 months))
- Biological objective : To evaluate the consequence of osimertinib treatment on the expression of targets of immune check point inhibitors(At baseline and at clinical disease progression (approximately 22 months))
- Biological objective : To demonstrate that the early kinetics of ctDNA is an indicator of response to osimertinib(At baseline and monthly until clinical disease progression (approximately 22 months))
- Biological objective : To observe if the presence of ctDNA at baseline is a prognostic factor of clinical progression disease(At baseline and monthly until clinical disease progression (approximately 22 months))
- Biological objective : To measure the biological progression (bPFS) in patients treated with osimertinib(At baseline and monthly until clinical disease progression (approximately 22 months))
- Biological objective : To compare the kinetic of appearance of EGFR mutation and radiological and clinical progression disease(At baseline and monthly until clinical disease progression (approximately 22 months))