A Prospective, Multi-center, Interventional Study of Osimertinib Combined With Anlotinib in Acquired EGFR T790M Mutated NSCLC Patients With Gradual Progression on Osimertinib Treatment
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 3
- 试验地点
- 2
- 主要终点
- progression-free survival (PFS)
研究概览
简要总结
EGFR T790M gatekeeper mutation accounts for approximately 60% of acquired resistance to the first- or second-generation EGFR-TKI treatment. Osimertinib, a third-generation EGFR TKI, has become the standard therapy for NSCLC patients with acquired EGFR T790M mutation. However, acquired resistance to osimertinib is still inevitable and there is no established targetable agent currently. Thus, treatment strategy for patients with acquire resistance to osimertinib remains an urgent issue. In this study, we aimed to evaluate the efficacy of osimertinib combined with anlotinib in acquired EGFR T790M mutated NSCLC patients with gradual progression on osimertinib treatment.
详细描述
In current clinical practice, acquired resistance to osimertinib can be divided into three clinical modes: dramatic progression, gradual progression and local progression. For patients with gradual progression,there are various clinical explorations，including the continuation of osimertinib with chemotherapy or radiotherapy, osimertinib combined with antiangiogenic agents. In preclinical studies, an overactive vascular endothelial growth factor/vascular endothelial growth factor receptor (VEGF/VEGFR) pathway and tumour angiogenesis plays a crucial role in the resistance to EGFR-TKIs, and the dual targeting of both the VEGF and EGFR pathways may prevent resistance.
Anlotinib (AL3818) is an inhibitor targeting multiple receptor tyrosine kinases involved in tumour progression, especially VEGFR 2/3, PDGFRα/β and c-Kit. We suppose that the combination treatment of osimertinib and anlotinib may ameliorate acquired resistance to osimertinib.This is a multi-center, open, single-arm, exploratory phase 2 trial evaluating osimertinib combined with anlotinib in acquired EGFR T790M mutated NSCLC patients with gradual progression on osimertinib 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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Ability to provide informed consent, complete all study assessments and have complete medical record.
- •Age:18-75 years.
- •Histologically or cytologically confirmed diagnosis of local advanced or metastatic NSCLC.
- •Patients should be confirmed acquired EGFR T790M mutation and received osimertinib as the second line treatment, and they should have the following: (1) benefit from treatment with osimertinib initially ;(2) gradual progression on osimertinib treatment as defined by minor increment of tumor burden (≥10% but <20% in the sum of target lesions).
- •At least one measurable lesion as defined by lesions ≥10mm in long axis according to RECIST 1.1.
排除标准
- •Patients who will be or were involved in any other interventional antitumour clinical studies for locally advanced/metastatic NSCLC currently or previously.
- •Small cell lung cancer (including small lung cancer mixed with non-small cell lung cancer).
- •Patients at risk of bleeding.
- •Patients with renal dysfunction.
- •Uncontrolled severe hypertension.
- •Any concomitant condition evaluated by physicians which is not suitable for osimertinib or anlotinib treatment.
研究组 & 干预措施
osimertinib combined with anlotinib
干预措施: osimertinib mesylate tablets and anlotinib hydrochloride capsules (Drug)
结局指标
主要结局
progression-free survival (PFS)
时间窗: from the date of first dose of osimertinib until the date of disease progression，assessed up to 12 months.
PFS is defined as the time from beginning of osimertinib to disease progression on combination treatment of osimertinib and anlotinib.
次要结局
- Objective Response Rate (ORR)(from the date of combination of osimertinib and anlotinib, assessed up to 6 weeks.)
- Adverse events/Serious adverse events(From signing ICF to 30 days after the end of treatment.)
- Disease Control Rate (DCR)(from the date of combination of osimertinib and anlotinib, assessed up to 6 weeks.)