A Phase IB/II, Open Label, Multicenter Study of INC280 Administered Orally in Combination With Gefitinib in Adult Patients With EGFR Mutated, c-MET-amplified Non-small Cell Lung Cancer Who Have Progressed After EGFR Inhibitor Treatment
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 161
- 试验地点
- 1
- 主要终点
- Phase Ib: Frequency of Dose Limiting Toxicities (DLTs)
研究概览
简要总结
This study assessed the safety and efficacy of escalating doses INC280 when added to gefitinib in patients with lung cancer that were known to have dysregulation of the c-MET pathway and who had failed after benefiting on a prior treatment with either gefitinib or erlotinib.
详细描述
The Phase Ib dose escalation part was aimed at the determination of the MTD/RP2D of capmatinib in combination with 250 mg gefitinib in patients with NSCLC patients with epidermal growth factor receptor (EGFR) mutation and cMET dysregulation and showing disease progression following EGFR tyrosine-kinase inhibitor (EGFR TKI) therapy. Dose escalation started with a dose of 100 mg/day to a maximum of 1200 mg/day, as capsule or tablet formulation. Successive cohorts of patients were to receive increasing doses of capmatinib in combination with a 250 mg once daily (qd) dose of gefitinib until the MTD/RP2D of capmatinib had been determined. The Phase II dose expansion part consisted of 400 mg capmatinib twice daily (bid), as either capsules or tablets, in combination with 250 mg gefitinib.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Documented EGFR mutation
- •Documented c-MET dysregulation
- •Prior clinical benefit on EGFR inhibitors and then subsequent progression
- •≥ 18 year old
- •Life expectancy of ≥ 3 months
- •ECOG performance status ≤ 2
排除标准
- •Unable to swallow tables once or twice daily
- •Previous treatment with c-MET inhibitor
- •Any unresolved toxicity from previous anticancer therapy greater than grade 1
- •History of cystic fibrosis
- •History of acute or chronic pancreatitis
- •Unable to undergo MRI or CT scans
- •Known history of HIV
- •Undergone a bone marrow or solid organ transplant
- •Clinically significant wound or lung tumor lesions with increased likelihood of bleeding
- •Pregnant or nursing
研究组 & 干预措施
INC280 200 mg Tab BID Phase Ib
tab=tablet; BID=twice daily
干预措施: Gefitinib (Drug)
INC280 100 mg Cap QD Phase Ib
cap=capsule; QD=once daily
干预措施: INC280 (Drug)
INC280 100 mg Cap QD Phase Ib
cap=capsule; QD=once daily
干预措施: Gefitinib (Drug)
INC280 200 mg Cap QD Phase Ib
cap=capsule; QD=once daily
干预措施: INC280 (Drug)
INC280 200 mg Cap QD Phase Ib
cap=capsule; QD=once daily
干预措施: Gefitinib (Drug)
INC280 400 mg Cap QD Phase Ib
cap=capsule; QD=once daily
干预措施: INC280 (Drug)
INC280 400 mg Cap QD Phase Ib
cap=capsule; QD=once daily
干预措施: Gefitinib (Drug)
INC280 800 mg Cap QD Phase Ib
cap=capsule; QD=once daily
干预措施: INC280 (Drug)
INC280 800 mg Cap QD Phase Ib
cap=capsule; QD=once daily
干预措施: Gefitinib (Drug)
INC280 200 mg Cap BID Phase Ib
cap=capsule; BID=twice daily
干预措施: INC280 (Drug)
INC280 200 mg Cap BID Phase Ib
cap=capsule; BID=twice daily
干预措施: Gefitinib (Drug)
INC280 400 mg Cap BID Phase Ib
cap=capsule; BID=twice daily
干预措施: INC280 (Drug)
INC280 400 mg Cap BID Phase Ib
cap=capsule; BID=twice daily
干预措施: Gefitinib (Drug)
INC280 600 mg Cap BID Phase Ib
cap=capsule; BID=twice daily
干预措施: INC280 (Drug)
INC280 600 mg Cap BID Phase Ib
cap=capsule; BID=twice daily
干预措施: Gefitinib (Drug)
INC280 200 mg Tab BID Phase Ib
tab=tablet; BID=twice daily
干预措施: INC280 (Drug)
INC280 400 mg Tab BID Phase Ib
tab=tablet; BID=twice daily
干预措施: INC280 (Drug)
INC280 400 mg Tab BID Phase Ib
tab=tablet; BID=twice daily
干预措施: Gefitinib (Drug)
INC280 400 mg Cap BID Phase II
cap=capsule; BID=twice daily
干预措施: INC280 (Drug)
INC280 400 mg Cap BID Phase II
cap=capsule; BID=twice daily
干预措施: Gefitinib (Drug)
INC280 400 mg Tab BID Phase II
tab=tablet; BID=twice daily
干预措施: INC280 (Drug)
INC280 400 mg Tab BID Phase II
tab=tablet; BID=twice daily
干预措施: Gefitinib (Drug)
结局指标
主要结局
Phase Ib: Frequency of Dose Limiting Toxicities (DLTs)
时间窗: Up to 215 weeks
A dose-limiting toxicity (DLT) was defined as an adverse event or abnormal laboratory value assessed as unrelated to disease progression, inter-current illness, or concomitant medications that met certain criteria as defined in the protocol.
Phase II : Overall Response Rate (ORR)
时间窗: Until disease progression, up to 60.8 weeks
Overall response rate is defined as the proportion of patients with best overall response (BOR) of complete response (CR) or partial response (PR), as per RECIST 1.1 (Overall Response (OR) = CR + PR). Complete Response (CR): Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm Partial Response (PR): At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
次要结局
- Phase Ib and II: Number of Participants With Adverse Events (AEs)(Up to 421 weeks)
- Phase Ib and II: Number of Participants With Serious Adverse Events (SAEs)(Up to 421 weeks)
- Phase Ib and II: Number of Patients With Dose Reductions of INC280 by Dose Level(Up to 417 weeks)
- Phase II: Duration of Response (DoR)(Up to 23.2 months)
- Phase I: PK Parameters AUCtau of INC280 and Gefitinib(Cycle 1 day 15 (pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 hours post dose) (Cycle=28 days))
- Phase I: PK Parameters Cmax of INC280 and Gefitinib(Cycle 1 day 15 (pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 hours post dose) (Cycle=28 days))
- Phase I: PK Parameters Tmax of INC280 and Gefitinib(Cycle 1 day 15 (pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 hours post dose) (Cycle=28 days))
- Phase Ib and II: Number of Patients With Dose Interruptions of Gefitinib by Dose Level(Up to 417 weeks)
- Phase II: Overall Survival (OS)(From date of treatment until death due to any cause, up to 70.2 months)
- Phase II: Progression Free Survival (PFS)(Up to 60.8 months)
- Phase I: PK Parameters Apparent Systemic Plasma Clearance Rate of INC280 and Gefitinib(Cycle 1 day 15 (pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 hours post dose) (Cycle=28 days))
- Phase I: PK Parameters Half-life of INC280 and Gefitinib(Cycle 1 day 15 (pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 hours post dose)(Cycle=28 days))