A Multi-Center, Phase 1/1b, Open-Label, Dose Escalation Study of ABT-700, a Monoclonal Antibody in Subjects With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 74
- 主要终点
- To evaluate the safety and tolerability of ABT-700 when administered as monotherapy and in combination with docetaxel or 5-fluoruracil, folinic acid, irinotecan and cetuximab (FOLFIRI/cetuximab) or erlotinib
研究概览
简要总结
This is a Phase 1/1b open-label study evaluating the safety, pharmacokinetics (PK), and preliminary efficacy of ABT-700 in subjects with advanced solid tumors that may have MET amplification or c-Met overexpression. ABT-700, previously known as h224G11 in publications, is an anti-c-Met antibody. The early clinical development plan for ABT-700 is based on the activity demonstrated in preclinical models. Up to 124 subjects will be enrolled.
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 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subject with advanced solid tumors; Dose-expansion: evidence for MET gene amplification.
- •Subject must have disease: a) that is not amenable to surgical resection, or b) that has progressed or recurred despite standard therapy, or c) that has failed to respond to standard therapy, or d) for which no effective therapy exists.
- •Subject cannot tolerate or must not be eligible for other approved therapeutic options with known survival advantage.
- •Subjects enrolled on the combination therapy phase must satisfy the above inclusion criteria and also the following: Subjects must have inoperable, locally advanced or metastatic cancer and be eligible to receive docetaxel or FOLFIRI/cetuximab or erlotinib in combination with ABT-700.
排除标准
- •Subject has received anticancer therapy including chemotherapy, immunotherapy, radiation therapy, immunotherapy, biologic, or any investigational therapy within a period of 21 days, or herbal therapy within 7 days prior to the first dose of ABT-
- •Subjects with uncontrolled metastases of the central nervous system. Subjects with brain metastases are eligible provided they have shown clinical and radiographic stable disease after definitive therapy and have not used steroids for at least 1 month prior to first dose of ABT-
- •Subject has unresolved adverse events > Grade 1 from prior anticancer therapy except for alopecia or anemia.
- •Subject has had major surgery within 21 days prior to the first dose of ABT-
- •Subjects enrolled on the combination therapy phase must not meet the above exclusion criteria and must be eligible to receive docetaxel or FOLFIRI/cetuximab or erlotinib per most current prescribing information, or at the discretion of the Investigator. Subjects with K-Ras mutation-positive colorectal cancer will be excluded from receiving FOLFIRI/cetuximab.
研究组 & 干预措施
Cohort C
ABT-700 plus FOLFIRI/cetuximab
干预措施: ABT-700 (Drug)
Cohort A
ABT-700 will be administered by intravenous infusion at escalating dose levels in 21-day dosing cycles. Additional subjects will be enrolled in an expansion cohort that will further evaluate ABT-700.
干预措施: ABT-700 (Drug)
Cohort B
ABT-700 plus docetaxel.
干预措施: ABT-700 (Drug)
Cohort B
ABT-700 plus docetaxel.
干预措施: docetaxel (Drug)
Cohort C
ABT-700 plus FOLFIRI/cetuximab
干预措施: FOLFIRI (Drug)
Cohort C
ABT-700 plus FOLFIRI/cetuximab
干预措施: cetuximab (Drug)
Cohort D
ABT-700 plus erlotinib
干预措施: ABT-700 (Drug)
Cohort D
ABT-700 plus erlotinib
干预措施: erlotinib (Drug)
结局指标
主要结局
To evaluate the safety and tolerability of ABT-700 when administered as monotherapy and in combination with docetaxel or 5-fluoruracil, folinic acid, irinotecan and cetuximab (FOLFIRI/cetuximab) or erlotinib
时间窗: First cycle of treatment through 60 day follow-up visit
Evaluation of vital signs, clinical lab testing, physical exams and adverse event monitoring
To determine the recommended Phase 2 dose for ABT-700
时间窗: First cycle of treatment through 60 day follow-up visit
To Evaluate the pharmacokinetics of ABT-700 when administered as monotherapy and in combination with docetaxel or 5-fluoruracil, folinic acid, irinotecan and cetuximab (FOLFIRI/cetuximab) or erlotinib
时间窗: At each cycle of treatment through 60 days after last dose.
Pharmacokinetic profile of ABT-700 analyzed from blood samples
次要结局
- To evaluate the preliminary efficacy of ABT-700 when administered as monotherapy and in combination with docetaxel or 5-fluoruracil, folinic acid, irinotecan and cetuximab (FOLFIRI/cetuximab) or erlotinib(Screening through 60 day follow-up visit)