A Phase II, Open Label, Single-arm Study to Assess the Safety and Efficacy of AZD9291 in Asia Pacific Patients With Locally Advanced/Metastatic Non-Small Cell Lung Cancer Whose Disease Has Progressed With Previous Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy and Whose Tumours Harbour a T790M Mutation Within the Epidermal Growth Factor Receptor Gene.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 171
- 试验地点
- 30
- 主要终点
- ORR According to RECIST 1.1 by Independent Review
研究概览
简要总结
A Phase II, Open Label, Single-arm Study to Assess the Safety and Efficacy of AZD9291 in Asia Pacific Patients with Locally Advanced/Metastatic Non-Small Cell Lung Cancer whose Disease has Progressed with Previous Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy and whose Tumours harbour a T790M mutation within the Epidermal Growth Factor Receptor Gene
详细描述
This is a phase II, open label, single arm study assessing the safety and efficacy of AZD9291 (80 mg, orally, once daily) in Asia Pacific patients with a confirmed diagnosis of Epidermal Growth Factor Receptor (EGFR) sensitising mutation positive (ie, G719X, exon 19 deletion, L858R, L861Q) and T790M mutation positive (hereafter referred to as EGFRm+ and T790M+) un-resectable, locally advanced or metastatic NSCLC (Stage IIIB-IV), who have progressed on an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor(EGFR-TKI), either as first line treatment or following one line of EGFR-TKI and one line of platinum containing doublet chemotherapy. Patients must agree to provide a biopsy for central confirmation of T790M mutation status following confirmed disease progression on the most recent treatment regimen. The primary objective of the study is to assess the efficacy of AZD9291 by assessment of Objective Response Rate according to RECIST 1.1 by an Independent Central Review.
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
- •Aged at least 18 years. Patient from Asia Pacific will be enrolled only.
- •Locally advanced or metastatic NSCLC, not amenable to curative surgery or radiotherapy.
- •Radiological documentation of disease progression on the last treatment administered prior to enrolling in the study: following 1st line EGFR TKI treatment but who have not received further treatment OR following prior therapy with an EGFR TKI and a platinum-based doublet chemotherapy. Patients may have also received additional lines of treatment.
- •Documented EGFR mutation (at any time since the initial diagnosis of NSCLC) known to be associated with EGFR TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q).
- •Patients must have central confirmation of tumour T790M mutation positive status from a biopsy sample taken after confirmation of disease progression on the most recent treatment regimen.
- •World Health Organisation (WHO) performance status 0-1 with no deterioration over the previous 2 weeks and a minimum life expectancy of 12 weeks.
- •At least one lesion, not previously irradiated and not chosen for biopsy during the study screening period, that can be accurately measured at baseline as ≥10mm in the longest diameter (except lymph nodes which must have short axis ≥15mm) with computerised tomography (CT) or magnetic resonance imaging (MRI) which is suitable for accurate repeated measurements.
- •Females of child-bearing potential using contraception and must have a negative pregnancy test.
排除标准
- •Treatment with an EGFR-TKI (eg, erlotinib, gefitinib, icotinib or afatinib) within 8 days or approximately 5x half-life of study entry; any cytotoxic chemotherapy, investigational agents or other anticancer drugs within 14 days of study entry; previous treatment with AZD9291 or a 3rd generation EGFR TKIs; Major surgery within 4 weeks of study entry; radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of study entry; currently receiving treatment with potent inhibitors or inducers of CYP3A
- •Any unresolved toxicities from prior therapy.
- •Unstable spinal cord compression or brain metastases.
- •Severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses or infection.
- •Refractory nausea and vomiting, chronic gastrointestinal diseases or bowel resection.
- •Cardiac disease.
- •Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease.
- •Inadequate bone marrow reserve or organ function.
研究组 & 干预措施
AZD9291
Once daily tablet 80 mg
干预措施: AZD9291 (Drug)
结局指标
主要结局
ORR According to RECIST 1.1 by Independent Review
时间窗: At baseline and every 6 weeks from time of first dose until objective disease progression,up to 24 months after Last Patient First Dose(LPFD)
Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT: Complete Response (CR): Disappearance of all target and non-target lesions and no new lesions; Partial Response (PR): \>= 30% decrease in the sum of diameters of Target Lesions (compared to baseline) and no new lesions. ORR is the percentage of patients with at least 1 visit response of CR or PR (according to independent review) that was confirmed at least 4 weeks later, prior to progression or further anti-cancer therapy.
次要结局
- DoR According to RECIST 1.1 by Independent Review(At baseline and every 6 weeks from time first dose until date of progression, up to 24 months after LPFD.)
- DCR According to RECIST 1.1 by Independent Review(At baseline and every 6 weeks from time first dose until date of progression, up to 24 months after Last Patient First Dose(LPFD))
- Tumour Shrinkage According to RECIST 1.1 by Independent Review(At baseline and every 6 weeks from time of first dose until date of progression, up to 24 months after LPFD.)
- PFS According to RECIST 1.1 by Independent Review(At baseline and every 6 weeks from time of first dose until objective disease progression, up to 24 months after LPFD.)
- Overall Survival (OS)(From first dose to end of study or date of death from any cause, whichever comes first, assessed every 6 weeks up to approximately 95 OS events (about 55% maturity) have been observed out of all enrolled patients.)