Phase II Trial of Neoadjuvant and Adjuvant Capmatinib in Participants With Stages IB-IIIA, N2 and Selected IIIB (T3N2 or T4N2) NSCLC With MET Exon 14 Skipping Mutation or High MET Amplification (Geometry-N)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 4
- 试验地点
- 6
- 主要终点
- Major Pathological Response (MPR) Rate
研究概览
简要总结
This study was planned to determine if neoadjuvant capmatinib could improve the major pathological response (MPR) in patients with Stage IB-IIIA, N2 and selected IIIB (T3N2 or T4N2) lung cancers with Mesenchymal Epithelial Transition (MET) exon 14 mutations and/or high MET amplification beyond those achieved with surgery, chemotherapy, and radiation. Treatment was to be continued with capmatinib in the adjuvant setting to evaluate the potential clinical benefit of extended therapy.
The purpose of this study is to determine if neoadjuvant capmatinib can improve outcomes in participants with stages I-IIIA non-small cell lung cancer with MET exon 14 mutations and/or high MET amplification beyond those achieved with surgery, chemotherapy, and radiation.
详细描述
This was a Phase II, two cohort, two stage study of capmatinib given for 8 weeks (2 cycles) prior to surgical resection, followed by three-year capmatinib treatment in adjuvant setting. Surgery had to be performed up to 2 weeks after the last dose of neoadjuvant study treatment.
There were 2 molecularly defined cohorts enrolled in parallel:
- Cohort A: MET exon 14 skipping mutations, irrespective of MET GCN or
- Cohort B: high level MET amplification (MET: GCN ≥ 10 by FISH or FoundationOne CDx NGS using tumor tissue).
Approximately 42 participants were aimed to be enrolled in the study, with 21 participants per cohort. This was planned to obtain 38 evaluable participants, 19 per each cohort. Participants who had both MET exon 14 skipping mutations and high-level MET amplification were planned to be enrolled into Cohort A. An evaluable subject received the neoadjuvant treatment and subsequently underwent surgery, resulting in a pathological response.
The study recruitment was prematurely discontinued due to significant recruitment challenges leading to termination of the study. The challenges included the rarity of the mutation and site initiation delays caused by staff shortages associated with COVID-19. As a result, only 4 subjects were enrolled and treated in Cohort A.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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 90 Years（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
Cohort A (MET exon 14 skipping mutations)
The study treatment started on Cycle 1 Day 1 with the first administration of capmatinib 400 mg twice a day (b.i.d.). The participants were planned to receive study treatment for a maximum of 3 years following surgery or until early discontinuation.
干预措施: capmatinib (Drug)
Cohort B (high MET amplification)
The study treatment started on Cycle 1 Day 1 with the first administration of capmatinib 400 mg twice a day (b.i.d.). The participants were planned to receive study treatment for a maximum of 3 years following surgery or until early discontinuation.
干预措施: capmatinib (Drug)
结局指标
主要结局
Major Pathological Response (MPR) Rate
时间窗: Baseline up to time of surgery (approximately 8 to 10 weeks after first dose)
The primary efficacy variable was MPR rate, defined as the proportion of participants with ≤ 10% residual viable cancer cells. MPR rate was to be assessed via local review for primary analysis. MPR assessment in tumor samples was collected at time of resection. Due to low number of participants and limited data, analysis related to the primary endpoint was not performed.
次要结局
- Overall Response Rate (ORR)(Baseline up to time of surgery (approximately 8 - 10 weeks after first dose))
- Complete Pathologic Response (pCR) Rate(Baseline up to time of surgery (approximately. 8- 10 weeks after first dose))
- Disease Free Survival (DFS)(From time of surgery to Months 24, 36, and 60)
- Number of Adverse Events and Serious Adverse Events as Assessed by CTCAE Criteria(Baseline up to 30 days after last dose of study medication, assessed up to approximately 20 months)