A Phase Ib/II, Open-label, Multicenter Trial With Oral cMET Inhibitor INC280 Alone and in Combination With Erlotinib Versus Platinum With Pemetrexed in Adult Patients With EGFR Mutated, cMET-amplified, Locally Advanced/Metastatic Non-small Cell Lung Cancer (NSCLC) With Acquired Resistance to Prior EGFR Tyrosine Kinase Inhibitor (EGFR TKI)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 23
- 试验地点
- 7
- 主要终点
- Phase Ib: Frequency and characteristics of Dose Limiting Toxicity (DLTs) to the INC280 and erlotinib combination
研究概览
简要总结
The purpose of this study was to determine the maximum tolerated dose (MTD) or recommended phase II dose (RP2D) of INC280 in combination with erlotinib in the Phase Ib of this study, and to assess the anti-tumor activity and safety of INC280 alone, and in combination with erlotinib, versus platinum with pemetrexed in the Phase II of this study, in adult patients with EGFR mutated, cMET amplified, advanced/metastatic non-small cell lung cancer with acquired resistance to prior EGFR TKI.
详细描述
The decision was taken to halt study enrollment with Cohort #3 in Phase Ib. Therefore, activities for the planned Phase II were not initiated.
This decision to stop further development of this combination was taken due to the challenge for enrollment in this very rare patient population along with the rapidly evolving disease landscape setting.
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
盲法说明
The study started as a non-randomized study, and was to move into randomized part in phase II. However the study was stopped after cohort #3 in the phase I part and so never moved into phase II.
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
- •Locally advanced or metastatic NSCLC
- •EGFR mutation (L858R and /or ex19del)
- •cMET amplification by FISH (GCN ≥ 6),
- •Acquired resistance to EGFR TKI (1st or 2nd generation)
- •ECOG performance status (PS) ≤ 1.
排除标准
- •Prior treatment with 3rd generation TKI
- •PhaseII : Prior treatment with any of the following agents:
- •Crizotinib, or any other cMET inhibitor or HGF-targeting inhibitor.
- •Concomitant EGFR TKI and platinum based chemotherapy as first line regimen.
- •Platinum-based chemotherapy as first line treatment
研究组 & 干预措施
INC280 200mg BID + ERL 150mg QD
Subjects who took INC280 200mg twice a day (BID) in combination with erlotinib (ERL) 150mg one a day (QD)
干预措施: INC280 single agent (Drug)
INC280 200mg BID + ERL 150mg QD
Subjects who took INC280 200mg twice a day (BID) in combination with erlotinib (ERL) 150mg one a day (QD)
干预措施: erlotinib (Drug)
INC280 400mg BID + ERL 150mg QD
Subjects who took INC280 400mg twice a day (BID) in combination with erlotinib (ERL) 150mg one a day (QD)
干预措施: INC280 single agent (Drug)
INC280 400mg BID + ERL 150mg QD
Subjects who took INC280 400mg twice a day (BID) in combination with erlotinib (ERL) 150mg one a day (QD)
干预措施: erlotinib (Drug)
结局指标
主要结局
Phase Ib: Frequency and characteristics of Dose Limiting Toxicity (DLTs) to the INC280 and erlotinib combination
时间窗: First 28 days of dosing
To determine MTD and/or RP2D of INC280 in combination with erlotinib
次要结局
- Phase Ib: Duration of Response (DOR)(Every 6 weeks, up to 2 years)
- Phase Ib: Number of patients with adverse events (AEs) as a measure of safety and tolerability(Every 3 weeks, up to 2 years)
- Phase Ib: Disease Control Rate (DCR)(Every 6 weeks, up to 2 years)
- Phase Ib: Overall response rate (ORR)(Every 3 weeks, up to 5 years)
- Phase Ib: Progression-free Survival (PFS)(Every 6 weeks, up to 2 years)
- Phase Ib: Plasma concentration-time profiles of INC280 and pharmacokinetic parameters(6 weeks)
- Phase Ib: Plasma concentration-time profiles of erlotinib in the presence of INC280(6 weeks)