A Phase I, Open-Label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Anti-tumour Activity of Gefitinib in Combination With MEDI4736 (Anti PD-L1) in Subjects With Non-Small Cell Lung Cancer(NSCLC)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 56
- 试验地点
- 1
- 主要终点
- Escalation Phase: safety and tolerability: AEs, laboratory data, vital signs, ECG changes and Echo. Expansion Phase: safety and tolerability of the recommended dose for MEDI4736; AEs, laboratory data, vital signs, ECG changes and Echo.
研究概览
简要总结
This a Phase I, Open-Label, Multicentre Study to assess the safety, tolerability, pharmacokinetics and preliminary anti-tumour activity of gefitinib in combination with MEDI4736 (anti PD-L1) in Subjects with Non-small cell lung cancer (NSCLC). The study consists of two phases: Escalation phase and an expansion phase to be conducted in locally advanced or metastatic NSCLC subjects
详细描述
In Escalation phase: MEDI4736 and gefitinib in NSCLC subjects In Expansion phase: Subjects with EGFR mutation positive locally advanced or metastatic NSCLC will be enrolled in expansion arms. Initiation of expansion arms with the recommended dose of MEDI4736 in combination with gefitinib will be based on an adequate safety and tolerability profile of the combination from the escalation phase.
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
- 18 Years 至 130 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Provision of signed and dated, written informed consent
- •Male or female aged 18 years and older.
- •Subjects must have a. In the escalation phase, locally advanced or metastatic NSCLC subjects who have either failed to respond or relapsed following any line of standard treatment, were unable to tolerate, or were not eligible for standard treatment b. In the expansion phase, histologically or cytologically confirmed locally advanced or metastatic NSCLC that is EGFR mutation positive, naïve to EGFR TKI therapy, and sensitive to EGFR TKIs therapy
- •a.For Escalation Phase: At least one lesion (measurable and/or non-measurable) b.For Expansion Phase: At least one measurable lesion.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •For Japan Escalation - the same as the global escalation I/E criteria except patients must be EGFR mutation positive
排除标准
- •Any concurrent chemotherapy, immunotherapy, biologic, or hormonal therapy for cancer treatment.
- •Any investigational agent, chemotherapy, immunotherapy, biologic, hormonal within 28 days of the first dose of study treatment
- •Inadequate bone marrow reserve or organ function
研究组 & 干预措施
Escalation
MEDI4736 will be combined with gefitinib to assess safety and tolerability
干预措施: Gefitinib (Drug)
Escalation
MEDI4736 will be combined with gefitinib to assess safety and tolerability
干预措施: MEDI4736 (Drug)
Expansion Arm
MEDI4736 will be combined with gefitinib
干预措施: Gefitinib (Drug)
Expansion Arm
MEDI4736 will be combined with gefitinib
干预措施: MEDI4736 (Drug)
结局指标
主要结局
Escalation Phase: safety and tolerability: AEs, laboratory data, vital signs, ECG changes and Echo. Expansion Phase: safety and tolerability of the recommended dose for MEDI4736; AEs, laboratory data, vital signs, ECG changes and Echo.
时间窗: From first dose of study treatment until 90 days after the last dose, assessed up to 32 months
AEs: Type, incidence, severity, seriousness and relationship to study medications of adverse events (AE) (graded by the National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events \[CTCAE\]; Safety Labs: Blood and urine samples for determination of clinical chemistry, hematology, coagulation, thyroid function tests and urinalysis will be taken at the visits; any laboratory abnormalities, and including dose-limiting toxicities (DLTs), ECG measurements and Creatinine Clearance
次要结局
- To obtain a preliminary assessment of the anti-tumour activity of gefitinib in combination with MEDI4736 by evaluation of tumour response(From baseline assessment to disease progression, assessed up to 30 months)
- To determine the immunogenicity of MEDI4736 in combination with gefitinib: anti-drug antibodies (ADAs)(From first dose of study treatment until 90 days after the last dose, assessed up to 32 months)
- To determine the pharmacokinetics of MEDI4736(From first dose of study treatment until 90 days after the last dose, assessed up to 32 months)
- To assess MEDI4736 pharmacodynamics in subjects receiving MEDI4736 in combination with gefitinib.(From first dose of study treatment until 90 days after the last dose, assessed up to 32 months)
- To determine overall survival (OS) in expansion Arm 1 and Arm 1a patients(From final safety follow-up visit after last dose until 1 year after the final patient discontinues investigational product (initial Medi4736).)