A Phase I, Open-Label, Multicentre Study to Evaluate the Safety, Tolerability and Pharmacokinetics of MEDI4736 in Patients With Advanced Solid Tumours
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 269
- 试验地点
- 1
- 主要终点
- Number of participants experiencing dose-limiting toxicities, adverse events (AEs), serious adverse events (SAEs)
研究概览
简要总结
This is a phase I, open-label, multicentre study of MEDI4736 administered intravenously with a standard 3+3 dose-escalation phase to evaluate safety, tolerability, and pharmacokinetics in patients with advanced solid tumor followed by an expansion phase in patients with advanced solid tumors.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 130 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •In the dose-escalation phase: patients with advanced solid tumors refractory to standard treatment, intolerant of standard treatment, or for which no standard therapy exists.
- •In the dose-expansion phase: histologically- or cytologically-confirmed advanced or metastatic biliary tract cancer (BTC), esophagus cancer(EC) (squamous cell carcinoma) or squamous cell carcinoma of the head and neck (SCCHN). - men or women. - Eastern Cooperative Oncology Group (ECOG) status of 0 or
- •Adequate organ and marrow function. - Subjects must have at least 1 measurable lesion. - Available archived tumor tissue sample. - Willingness to provide consent for biopsy samples.
排除标准
- •Any prior Grade ≥ 3 irAE while receiving immunotherapy - Prior exposure to any anti-PD-1 or anti-PD-L1 antibody - Active or prior documented autoimmune disease within the past 2 years - History of primary immunodeficiency - Symptomatic or untreated central nervous system (CNS) metastases requiring concurrent treatment - Women who are pregnant or lactating - Uncontrolled intercurrent illness - Known history of tuberculosis - Known to be human immunodeficiency virus (HIV) positive - Hepatitis B or C infection - Other invasive malignancy within 5 years
研究组 & 干预措施
MEDI4736 Q2W
Evaluate MEDI4736 given every 2 weeks
干预措施: MEDI4736 (Drug)
MEDI4736 Q3W
Evaluate MEDI4736 given every 3 weeks
干预措施: MEDI4736 (Drug)
MEDI4736 Dose Expansion
evaluate MEDI4736 given every 2 weeks
干预措施: MEDI4736 (Drug)
MEDI4736 Q4W
Evaluate MEDI4736 given every 4 weeks
干预措施: MEDI4736 (Drug)
MEDI4736 combined with another drug
evaluate MEDI4736 in combination with another drug given every 4 weeks
干预措施: tremelimumab (Drug)
结局指标
主要结局
Number of participants experiencing dose-limiting toxicities, adverse events (AEs), serious adverse events (SAEs)
时间窗: 90 days after the last dose of MEDI4736
Safety profile will be assessed through number of participants experiencing adverse events (AEs), serious adverse events (SAEs), laboratory evaluations, vital signs, and physical examinations.
次要结局
- Area under the concentration of MEDI4736 time curve(Up to 90 days after the last dose of MEDI4736)
- Percentage of participants who developed detectable anti-drug antibodies (ADAs).(Up to 6 months after the last dose of MEDI4736 or up to 1 month after the last dose of tremelimumab where applicable.)
- Objective response rate (ORR)(From first dose of study drug until death or up to 2 years)
- Maximum tolerated dose (MTD) or optimal biological dose (OBD)(90 days after the last dose of MEDI4736)
- Maximum concentration of MEDI4736(Up to 90 days after the last dose of MEDI4736)
- Clearance(Up to 90 days after the last dose of MEDI4736)
- half-life after administration of MEDI4736(Up to 90 days after the last dose of MEDI4736)
- Disease control rate (DCR)(From first dose of study drug until death or up to 2 years)
- Duration of response (DoR)(From first dose of study drug until death or up to 2 years)
- Progression-free survival (PFS)(From first dose of study drug until death or up to 2 years)
- Overall survival (OS)(From first dose of study drug until death or up to 2 years)