MEDI4736 (Anti PD-L1) Combined With Gefitinib in Subjects With Non-Small Cell Lung Cancer(NSCLC).
2022年3月22日 更新者：MedImmune LLC
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)
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
研究概览
详细说明
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.
研究类型
介入性
注册 (实际的)
56
阶段
- 阶段1
联系人和位置
本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。
参与标准
研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
18年 至 130年 (成人、年长者)
接受健康志愿者
不
有资格学习的性别
全部
描述
Key Inclusion Criteria:
- 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 1.
- For Japan Escalation - the same as the global escalation I/E criteria except patients must be EGFR mutation positive
Key Exclusion Criteria:
- 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
学习计划
本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：非随机化
- 介入模型：并行分配
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
|
实验性的：Escalation
MEDI4736 will be combined with gefitinib to assess safety and tolerability
|
Gefitinib QD
MEDI4736 IV Q2W
|
|
实验性的：Expansion Arm
MEDI4736 will be combined with gefitinib
|
Gefitinib QD
MEDI4736 IV Q2W
|
研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
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.
大体时间：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
|
From first dose of study treatment until 90 days after the last dose, assessed up to 32 months
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
To obtain a preliminary assessment of the anti-tumour activity of gefitinib in combination with MEDI4736 by evaluation of tumour response
大体时间：From baseline assessment to disease progression, assessed up to 30 months
|
At each visit subjects will be programmatically assigned a RECIST visit response of CR, PR, SD or PD depending on the status of their disease compared to baseline and previous assessments; Objective response rate: the percentage of subjects who have at least one visit response of CR or PR prior to any evidence of progression .
Disease control rate: the percentage of subjects who have at least one visit response of CR or PR or SD prior to any evidence of progression.
Progression Free Survival (PFS) : the time from start of study treatment to the first documentation of objective disease progression (PD) or death from any cause.
|
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)
大体时间：From first dose of study treatment until 90 days after the last dose, assessed up to 32 months
|
Assessed by evaluating the number and percentage of subjects who develop detectable anti-drug antibodies (ADAs).
The impact of ADAs on overall MEDI4736 PK will also be evaluated.
|
From first dose of study treatment until 90 days after the last dose, assessed up to 32 months
|
|
To determine the pharmacokinetics of MEDI4736
大体时间：From first dose of study treatment until 90 days after the last dose, assessed up to 32 months
|
Individual MEDI4736 concentrations will be tabulated by dose cohort along with descriptive statistics.
Noncompartmental PK data analysis will be performed
|
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.
大体时间：From first dose of study treatment until 90 days after the last dose, assessed up to 32 months
|
PD-L1 levels before and after treatment with MEDI4736 will be measured to evaluate its association with response to treatment with MEDI4736 and clinical outcome
|
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
大体时间：From final safety follow-up visit after last dose until 1 year after the final patient discontinues investigational product (initial Medi4736).
|
Survival information may be obtained via telephone contact with the patient, patients family or by checking the patients notes, hospital records, contacting the patients general practitioner or public death registry, where it is possible to do so under applicable local laws.
|
From final safety follow-up visit after last dose until 1 year after the final patient discontinues investigational product (initial Medi4736).
|
合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
合作者
调查人员
- 首席研究员：Sang-We Kim, MD、Asan Medical Center
- 首席研究员：Laura Chow, MD、University of Washington
- 首席研究员：Ben Creelan, MD、Moffit Cancer Center
- 首席研究员：Don Gibbons, MD、M.D. Anderson Cancer Center
- 首席研究员：Shinitaro Kanda, MD、National Cancer Center
- 首席研究员：Naoyuki Nogami、Shikoku Cancer Center
出版物和有用的链接
负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始 (实际的)
2014年3月24日
初级完成 (实际的)
2021年3月9日
研究完成 (实际的)
2021年3月9日
研究注册日期
首次提交
2014年3月7日
首先提交符合 QC 标准的
2014年3月12日
首次发布 (估计)
2014年3月14日
研究记录更新
最后更新发布 (实际的)
2022年4月4日
上次提交的符合 QC 标准的更新
2022年3月22日
最后验证
2022年3月1日
更多信息
与本研究相关的术语
关键字
其他相关的 MeSH 术语
其他研究编号
- D791PC00001
计划个人参与者数据 (IPD)
计划共享个人参与者数据 (IPD)？
是的
IPD 计划说明
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment:
https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
IPD 共享时间框架
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles.
For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
IPD 共享访问标准
When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool .
Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access.
For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.
Gefitinib的临床试验
-
Sichuan Provincial People's Hospital未知