A Phase 1b Open-label Study to Evaluate the Safety and Tolerability of MEDI4736 in Combination With Tremelimumab in Subjects With Advanced Non-small Cell Lung Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 459
- 试验地点
- 1
- 主要终点
- Objective response
研究概览
简要总结
The purpose of this study is to determine if MEDI4736 will be adequately tolerated in combination with tremelimumab in subjects with advanced non-small cell lung cancer (NSCLC).
详细描述
This is a multicenter, open-label, dose-escalation, and dose expansion study of MEDI4736 in combination with tremelimumab to evaluate the safety, tolerability, pharmacokinetic (PK), immunogenicity, and antitumor activity of MEDI4736 in combination with tremelimumab in adult subjects with advanced NSCLC.
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
- 18 Years 至 101 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years
- •Advanced non-small cell lung cancer
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
- •Adequate organ and marrow function
排除标准
- •Any concurrent chemotherapy, immunotherapy, biologic, or hormonal therapy for cancer treatment
- •Current or prior use of immunosuppressive medication within 14 days before the first dose of study drugs
- •Active or prior documented autoimmune disease within the last 2 years.
研究组 & 干预措施
Dose Escalation
MEDI4736 and tremelimumab received by intravenous infusion.
干预措施: MEDI4736 (Drug)
Dose Escalation
MEDI4736 and tremelimumab received by intravenous infusion.
干预措施: tremelimumab (Drug)
Arm A
Medi4736 and tremelimumab received by intravenous infusion
干预措施: MEDI4736 (Drug)
Arm A
Medi4736 and tremelimumab received by intravenous infusion
干预措施: tremelimumab (Drug)
Arm B
MEDI4736 and tremelimumab received by intravenous infusion
干预措施: MEDI4736 (Drug)
Arm B
MEDI4736 and tremelimumab received by intravenous infusion
干预措施: tremelimumab (Drug)
Arm C
MEDI4736 and tremelimumab received by intravenous infursion
干预措施: MEDI4736 (Drug)
Arm C
MEDI4736 and tremelimumab received by intravenous infursion
干预措施: tremelimumab (Drug)
结局指标
主要结局
Objective response
时间窗: At least 24 weeks as compared to baseline
Best overall response of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as defined as the best response among all overall responses recorded from the start of treatment until progression, or the last evaluable disease assessment in the absence of progressive disease (PD) prior to the initiation of subsequent anti-cancer therapy, or discontinuation from the study, whichever occurs first.
Number of subjects experiencing dose-limiting toxicities (DLTs)
时间窗: Depending upon the cohort, the DLT evaluation period is from the 1st dose of study medication until (1) the 3rd dose of MEDI4736 and tremelimumab (2) the 2nd dose of MEDI4736 and tremelimumab or (3) the 3rd dose of MEDI4736 and 2nd dose of tremelimumab
The maximum tolerated dose (MTD), which is the highest dose within a cohort where no more than 1 out of 6 subjects experience DLTs or the highest protocol-defined dose for each agent in the absence of exceeding the MTD, will be evaluated using the following safety assessments: adverse events, serious advents, laboratory evaluations, vital signs, physical examinations, and electrocardiogram (ECG) results. Measurements will be aggregated to determine whether a subject has experienced a DLT as assessed by the investigator.
Number of subjects reporting adverse events
时间窗: Screening through 90 days after the last dose of study medication
The number of subjects reporting adverse events (AEs) and number (percentage) of subjects reporting serious adverse events (SAEs) as graded by CTCAE Version 4.03
次要结局
- Immunogenicity of tremelimumab in combination with MEDI4736(During treatment through study completion, about 2 years)
- Antitumor activity of tremelimumab in combination with MEDI4736(During treatment through study completion, about 2 years)
- Pharmacokinetic parameters(During treatment through study completion, about 2 years)
- Number of subjects reporting adverse events(Screening through 90 days after the last dose of study medication)