A Phase I, Multi-center, Open-label, Single-dose Escalation and Expansion, Dose Escalation and Expansion Combination With Chemotherapy Study Evaluating the Safety, Tolerability and Pharmacokinetic Profile of M108 Monoclonal Antibody in Patients With Advanced Unresectable Solid Tumors in China
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 152
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose
研究概览
简要总结
M108 is a monoclonal antibody specific for gastric and gastroesophageal adenocarcinomas. The aim of this phase I study is to establish safety and Tolerability of different Dosage regimen in patients With Advanced Unresectable Solid Tumors in China.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent.
- •Advanced Unresectable solid tumors proven by histology
- •At least 1 measurable site of the disease according RECIST 1.1 criteria
- •ECOG performance status (PS) 0-1
- •Life expectancy > 3 months
- •Age ≥ 18 years and ≤75 years
- •Adequate haematological function; absolute neutrophil count ≥1.5 x 109/L; white blood cell count ≥3.0 x 109/L; platelets ≥100 x 109/L; haemoglobin ≥9 g/dL.
- •Adequate coagulation function; international normalized ratio ( INR) ≤ 1.5 x upper limit of normal (ULN), or activated partial thromboplastin time (APTT) ≤ 1.5 x ULN.
- •Adequate hepatic function; bilirubin ≤1.5 x ULN, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) ≤2.5 x ULN.
- •Adequate renal function; creatinine ≤1.5 x ULN, or reatinine clearance rate ≥60 mL/minute calculated.
排除标准
- •Previous received or planned to be vaccinated with 2019-nCoV vaccine or other vaccines within 3 months prior to the start of study treatment or during the study or within 3 months after the end of the study;
- •Previous radiotherapy within 4 weeks prior to the start of study treatment. (if palliative radiotherapy was given to bone metastatic side peripherally and the patient recovered from acute toxicity was allowed).
- •Previous anti-tumor therapy within 4 weeks prior to the start of study treatment.
- •Previous major operation within 8 weeks prior to the start of study treatment.
- •Prior severe allergic reaction or intolerance to a monoclonal antibody, including humanised or chimeric antibodies.
- •Symptomatic cerebral metastases.
- •Uncontrolled or severe illness.
- •Known human immunodeficiency virus infection or known symptomatic hepatitis
- •Other clinically significant disease which may have adversely affected the safe delivery of treatment within this study
研究组 & 干预措施
Dose Escalation Cohort
Monotherapy: Five dose levels of M108 will be tested according to an accelerated titration method followed by a conventional 3 + 3 study design.
Combined with chemotherapy: Three dose levels of M108 will be tested by a conventional 3 + 3 study design.
The dose-limiting toxicity (DLT) will be assessed from the first administration to the end of the first cycle (21 days).
干预措施: M108 (Drug)
Dose Expansion Cohort
Once the effective dose has been determined, 1~2 expansion cohorts will be opened to evaluate the efficacy and safety of the selected dose.
干预措施: M108 (Drug)
结局指标
主要结局
Maximum Tolerated Dose
时间窗: 21 days
MTD
Incidence of adverse events
时间窗: From enrollment until 28+7 days after the last dose
defined by the Common Terminology Criteria for Adverse Events version 5.0 (CTCAE V5.0)
次要结局
- Half-life of M108(From enrollment until 28 days after the last dose)
- Maximum measured plasma concentration of M108(From enrollment until 28 days after the last dose)
- Objective Response Rate(From first dose to disease progression , death or end of study，an average of 1 year)
- Time to maximum plasma concentration of M108(From enrollment until 28 days after the last dose)
- Immunogenicity profile of M108(From enrollment until 28 days after the last dose)
- Progression free survival(From first dose to disease progression , death or end of study，an average of 1 year)