Open Label, Multinational, Multicenter, Real World Treatment Study of Single Agent AZD9291 for Patients With Advanced/Metastatic Epidermal Growth Factor Receptor (EGFR) T790M Mutation-Positive Non-Small Cell Lung Cancer (NSCLC) Who Have Received Prior Therapy With an EGFR Tyrosine Kinase Inhibitor (EGFR-TKI)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 3,017
- 试验地点
- 1
- 主要终点
- Overall Survival (OS)
研究概览
简要总结
The aim of this study is to assess the efficacy and safety of single agent AZD9291 in a real world setting in adult patients with advanced or metastatic, epidermal growth factor receptor (EGFR) T790M mutation-positive Non-Small Cell Lung Cancer (NSCLC), who have received prior EGFR-tyrosine kinase inhibitor (TKI) therapy.
详细描述
Objective: The primary objective of this study is to assess the efficacy and safety of single agent AZD9291 in a real world setting in adult patients with advanced or metastatic, epidermal growth factor receptor (EGFR) T790M mutation-positive Non-Small Cell Lung Cancer (NSCLC), who have received prior EGFR-tyrosine kinase inhibitor (TKI) therapy.
Study site(s) and number of patients planned: Approximately 1500 patients will be recruited in Europe. The recruitment will be increased beyond that as the study will expand in other regions of the world (America, Asia).
Study Design This will be an open-label, single-arm, multinational, multicenter, real world treatment study.
Target patient population: Adult patients (fulfilling the definition of "age of majority" per local regulations) with locally advanced (stage IIIB) or metastatic (stage IV) NSCLC with confirmed T790M mutation, who have received prior EGFR-TKI therapy.
Investigational product (IP), dosage, and mode of administration: AZD9291 is an oral, potent, selective, irreversible inhibitor of both EGFR-TKI sensitising and resistance mutations in NSCLC with a significant selectivity margin over wild-type EGFR. AZD9291 will be administered orally as one 80 mg tablet once a day.
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 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 by the patient or legally acceptable representative prior to any study-specific procedures
- •Adults (according to each country regulations for age of majority)
- •Locally advanced (stage IIIB) or metastatic (stage IV) EGFRm NSCLC, not amenable to curative surgery or radiotherapy, with confirmation of the presence of the T790M mutation
- •Prior therapy with an EGFR-TKI. Patients may have also received additional lines of treatment
- •World Health Organization (WHO) performance status 0-2
- •Adequate bone marrow reserve and organ function as demonstrated by complete blood count, biochemistry in blood and urine at baseline (please refer to IB for guidance)
- •ECG recording at baseline showing absence of any cardiac abnormality as per exclusion criterion #6
- •Female patients of childbearing potential must be using adequate contraceptive measures, must not be breast feeding, and must have a negative pregnancy test prior to start of dosing. Otherwise, they must have evidence of nonchildbearing potential
- •Male patients must be willing to use barrier contraception, i.e., condoms
排除标准
- •Previous (within 6 months) or current treatment with AZD9291
- •Patients currently receiving (or unable to stop use at least 1 week prior to receiving the first dose of AZD9291) any treatment known to be potent inhibitors or inducers of cytochrome P450 (CYP) 3A4
- •Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension, active bleeding diatheses, active infection including hepatitis B, hepatitis C, and human immunodeficiency virus, or significantly impaired bone marrow reserve or organ function, including hepatic and renal impairment, which in the investigator's opinion would significantly alter the risk/benefit balance.
- •Patient with symptomatic central nervous system (CNS) metastases who is neurologically unstable or has required increasing doses of steroids to manage CNS symptoms within the 2 weeks prior to start AZD9291 administration;
- •Past medical history of ILD, drug-induced ILD, radiation pneumonitis requiring steroid treatment, or any evidence of clinically active ILD
- •Any of the following cardiac criteria:
- •Mean resting corrected QT interval (QTcF) > 470 ms using Fredericia's formula :
- •Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block, second degree heart block)
- •Any factors that increase the risk of QTc prolongation or risk of arrhythmic events
- •Any unresolved toxicity from prior therapy CTCAE > grade 3 at the time of starting treatment
- •History of hypersensitivity to excipients of AZD9291 or to drugs with a similar chemical structure or class to AZD9291
研究组 & 干预措施
AZD9291
Single arm of AZD9291, starting dose of 80mg
干预措施: T790M+ Testing (Procedure)
AZD9291
Single arm of AZD9291, starting dose of 80mg
干预措施: Baseline Visit Blood & Urine Testing (Procedure)
AZD9291
Single arm of AZD9291, starting dose of 80mg
干预措施: Baseline ECG (Procedure)
AZD9291
Single arm of AZD9291, starting dose of 80mg
干预措施: Visual Slit-Lamp Testing (Procedure)
AZD9291
Single arm of AZD9291, starting dose of 80mg
干预措施: AZD9291 Dosing (Drug)
结局指标
主要结局
Overall Survival (OS)
时间窗: From the date of first dose of Osimertinib until the date of death (due to any cause) or last participant contact [up to 43 months]
OS was defined as the time, in months from the date of first dose of Osimertinib until death due to any cause, or at last documented contact with participant status "alive" (in this study any participants alive at study discontinuation, or lost to follow-up was considered being censored at study discontinuation date or at the last known date participant was alive). OS was summarized using a Kaplan-Meier (KM) estimate of the median time to death or censoring together with their 95% confidence intervals.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: From screening to progression follow-up [every 6 weeks +/- 1 week] relative to the date of enrolment until the end of study [up to 43 months]
Safety assessment of Osimertinib was analyzed by evaluating AEs and SAEs.
次要结局
- Progression Free Survival(From the date of first dose of Osimertinib until disease progression or death in the absence of progression [up to 43 months])
- Time to Treatment Discontinuation (TTD)(From the date of first dose of Osimertinib until disease progression or death in the absence of progression [up to 43 months])
- Response Rate (RR)(From the date of first dose of Osimertinib until disease progression or death in the absence of progression [up to 43 months])