Phase 1 Study to Evaluate the Safety and Tolerability of the CD40 Agonistic Monoclonal Antibody APX005M in Subjects With Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 43
- 试验地点
- 3
- 主要终点
- Incidence of dose limiting toxicities
研究概览
简要总结
This study is a phase 1 open-label dose escalation study of the immuno-activating monoclonal antibody APX005M in adults with solid tumors. Study is intended to establish the maximum tolerated dose and the overall safety and tolerability of APX005M in 3 different administration schedules.
详细描述
APX005M-001 is an open-label study and comprises a dose-escalation portion of approximately 8 dose level cohorts, plus an expansion cohort.
Eligible subjects with solid tumors will receive intravenous APX005M every 3 week, every 2 week or every 1 week until disease progression, unacceptable toxicity or death, whichever occurs first.
Study objectives include:
- Evaluate safety of APX005M
- Determine the maximum tolerated dose of APX005M
- Determine the pharmacokinetic parameters of APX005M: the maximal drug concentration (Cmax), area under the curve of serum concentration over time (Area Under the Curve/ AUC), and half-life (t½).
- Preliminary assessment of clinical response
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Histologically documented diagnosis of solid tumor
- •For subjects in the every 2 week and every 1 week dosing cohorts histologically or cytologically documented diagnosis of urothelial carcinoma, melanoma, squamous cell carcinoma of the head and neck, non-small cell lung cancer, or any solid tumor with high microsatellite instability status (MSI-high)
- •No known effective therapy options are available
- •Measurable disease by RECIST 1.1
- •ECOG performance status of 0 or 1
- •Adequate bone marrow, liver and kidney function
- •No toxicities related to prior treatment related toxicities with the exception of alopecia and neuropathy
- •Negative pregnancy test for women of child bearing potential
排除标准
- •Any history of or current hematologic malignancy
- •Major surgery or treatment with any other investigational agent within 4 weeks
- •Uncontrolled diabetes or hypertension
- •History of arterial thromboembolic event
- •History of congestive heart failure, symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention, or myocardial infarction
- •Active known clinically serious infections
研究组 & 干预措施
APX005M every 3 week
Subjects receive APX005M intravenously every 3 week until disease progression, unacceptable toxicity or death.
干预措施: APX005M (Drug)
APX005M every 2 week
Subjects receive APX005M intravenously every 2 week until disease progression, unacceptable toxicity or death.
干预措施: APX005M (Drug)
APX005M every 1 week
Subjects receive APX005M intravenously every 1 week until disease progression, unacceptable toxicity or death.
干预措施: APX005M (Drug)
结局指标
主要结局
Incidence of dose limiting toxicities
时间窗: Up to 28 days following first dose of APX005M
The rate of DLTs will be assessed in approximately 56 subjects. DLTs will include Grade 4 neutropenia, anemia, thrombocytopenia, Grade 3or 4 nausea, cytokine release syndrome and other Grade 3 non-hematological toxicity
Incidence of adverse events
时间窗: Through up to approximately 4 weeks following last dose of APX005M
Incidence and severity of AEs and specific laboratory abnormalities graded according to NCI-CTCAE, v4.03
次要结局
- Objective response rate according to Response Evaluation Criteria in Solid Tumors (RECIST)(Every 8 weeks up to approximately 1 year following first dose of APX005M)
- Blood concentrations of APX005M(Predose, 0.5, 1, 2, 4, 24, 48 and 168 hours following first and third dose of APX005M)
- Presence and titer of anti-APX005M antibodies(Prior to first dose, approximately 3, 6 and 9 weeks following first dose and approximately 4 weeks following last dose of APX005M)