A Multicenter, Phase 1/2, Open-Label Study Evaluating the Tolerability, Safety, Pharmacokinetics, and Efficacy of AMG 337 in Asian Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 11
- 试验地点
- 1
- 主要终点
- Phase 1- Adverse events and clinical laboratory abnormalities
研究概览
简要总结
This is a multicenter, Phase 1/2 study. The study will evaluate the tolerability, safety and activity of AMG 337 in Asian subjects who have advanced solid tumors (Phase 1) or subjects with MET amplified tumors with a focus on gastric/gastroesophageal junction/esophageal adenocarcinoma (Phase 2).
详细描述
This is a Phase 1/2, multicenter, single arm, open-label study to assess the safety, efficacy and pharmacokinetics of AMG 337 in solid tumors. In the Phase 1, approximately 3 to 45 subjects enrolled in a 3+3+3 dose escalation scheme evaluating two dose levels. In the Phase 2, approximately 140 subjects will be enrolled to either Cohort 1 (subjects with MET amplified /gastroesophageal junction/esophageal (G/GEJ/E) adenocarcinoma with measurable tumor) or Cohort 2 (subjects with MET amplified solid tumors with measurable tumor and subjects with MET amplified G/GEJ/E adenocarcinoma with non-measurable tumor). All subjects will self-administer AMG 337 daily until disease progression or other protocol specified end of treatment criteria are met. Tumor assessment by RECIST 1.1 will be followed during study treatment.
Tumor tissue, biomarkers, pharmacokinetics and Patient Reported Outcomes will be assessed.
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
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Able to self administer daily AMG 337 as a whole capsule
- •Male or female 20 years of age or over
- •Phase 1: Subjects must have a pathologically confirmed, advanced solid tumor for which the subjects have received prior therapy for advanced disease, for which no standard therapy exists, or the subject refuses standard therapy.
- •Phase 2: Subjects must have a pathologically confirmed, advanced G/GEJ/E adenocarcinoma (cohort 1) or other solid tumor (cohort 2) for which the subjects have received prior therapy for advanced disease, or for which no standard therapy exists, or the subject refuses standard therapy.
- •Tumor MET amplified by protocol-specified centralized testing (phase 2 only).
- •Phase 1: Measurable or non-measurable disease per RECIST v1.1
- •Phase 2: Measurable disease per RECIST v1.1 guidelines. Cohort 2 may include subjects with advanced MET amplified G/GEJ/E adenocarcinoma with non-measurable tumor per RECIST v1.
- •(ECOG) Performance Status of 0, 1, or 2
- •Other protocol defined inclusion criteria may apply.
排除标准
- •Known central nervous system metastases.
- •Subject is a candidate for curative surgery or definitive chemoradiation.
- •Peripheral edema > grade
- •Subjects who have persistent gastric outlet obstruction, complete dysphagia or are dependent upon jejunostomy for feeding. Significant gastrointestinal disorder(s) that in the opinion of the Investigator may influence drug absorption.
- •Currently receiving any anti-tumor treatments, or less than 14 days prior to enrollment since ending anti-tumor treatment.
- •Prior treatment with small molecule inhibitors of the MET pathway.
- •Other protocol defined exclusion criteria may apply.
研究组 & 干预措施
Single arm
干预措施: AMG 337 (Drug)
结局指标
主要结局
Phase 1- Adverse events and clinical laboratory abnormalities
时间窗: 17 months
Adverse events and clinical laboratory abnormalities defined as DLTs.
Phase 2- Overall Response Rate (per RECIST v1.1) in subjects with MET amplified measurable gastric/gastroesophageal junction/esophageal adenocarcinoma (cohort 1)
时间窗: 17 months
Determine anti-tumor activity of AMG 337 in subjects with MET amplified gastric/gastroesophageal junction/esophageal adenocarcinoma (cohort 1)
次要结局
- Phase 2- Overall Response Rate (per RECIST v1.1) in subjects with other MET amplified solid tumors (subjects with measurable disease in cohort 2)(17 months)
- Phase 1- Duration of Response(17 months)
- Phase 1- Progression-Free Survival (per RECIST v1.1)(17 months)
- Phase 1- Pharmacokinetic parameters(17 months)
- Phase 2- Time to response (cohort 1 and subjects with measurable disease at baseline in cohort 2)(17 months)
- Phase 2- AMG 337 exposure and dose intensity(17 months)
- Phase 1- Overall Survival(17 months)
- Phase 1- Other adverse events, clinical laboratory abnormalities and ECG parameters(17 months)
- Phase 2- Overall Survival(17 months)
- Phase 1- Time to Response(17 months)
- Phase 2- Progression Free Survival(17 months)
- Phase 2- Incidence and severity of adverse events and significant laboratory abnormalities(17 months)
- Phase 2- Duration of Response (cohort 1 and subjects with measurable disease at baseline in cohort 2)(17 months)
- Phase 2- Pharmacokinetic parameters(17 months)
- Phase 1- Overall Response Rate(17 months)