A Phase III, Open Label, Randomized Study of AZD9291 Versus Platinum-Based Doublet Chemotherapy for Patients With Locally Advanced or 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 (AURA3).
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 421
- 试验地点
- 1
- 主要终点
- Progression Free Survival (PFS) by Investigator Assessment
研究概览
简要总结
A Phase III, Open Label, Randomized Study of Osimertinib versus Platinum-Based Doublet Chemotherapy for Patients with Locally Advanced or 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 III, open label, randomized study assessing Osimertinib (80 mg, orally, once daily) versus platinum-based doublet chemotherapy (standard of care) in subjects with confirmed diagnosis of Epidermal Growth Factor Receptor (EGFR) mutation positive NSCLC, who have progressed following prior therapy with an approved Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI) agent and whose tumours harbour a T790M mutation within the EGFR Gene. Subjects must be chemotherapy naive and must agree to provide a biopsy for central confirmation of T790 mutation status following confirmed disease progression on their first line EGFR-TKI treatment (e.g. erlotinib, gefitinib or afatinib). Suitable subjects will then be randomized to receive either Osimertinib (80mg orally, once daily) or platinum-based doublet chemotherapy (pemetrexed 500 mg/m2 + carboplatin area under the plasma concentration-time curve AUC 5 or pemetrexed 500 mg/m2 + cisplatin 75 mg/m2) on Day 1 of every 21-day cycle in a 2:1 (Osimertinib: platinum-based doublet chemotherapy) ratio. Once subjects on the platinum-based doublet chemotherapy arm are determined to have objective radiological progression according to RECIST 1.1 by the investigator and confirmed by independent central imaging review, they will be given the opportunity to begin treatment with Osimertinib 80mg, once daily. These subjects may continue treatment with Osimertinib even after disease progression, as long as they are continuing to show clinical benefit, as judged by the investigator. The primary objective of the study is to assess the efficacy of Osimertinib compared with platinum-based doublet chemotherapy by assessment of Progression Free Survival (PFS), using investigator assessments according to Response Evaluation Criteria in Solid Tumours (RECIST 1.1), as well as asensitivity analysis of Progression Free Survival using Blinded Independent Central Review (BICR).
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- •Subjects with histologically or cytologically documented NSCLC.
- •Locally advanced or metastatic NSCLC
- •Radiological documentation of disease progression following 1st line EGFR TKI Treatment without any further treatment
- •Eligible to receive treatment with the selected doublet-chemotherapy
- •Central confirmation of T790M+ mutation status
- •World Health Organization (WHO) performance status 0-1
- •At least one lesion, not previously irradiated.
排除标准
- •• Prior neo-adjuvant or adjuvant chemotherapy treatment within 6 months prior of starting 1st EGFR TKI treatment
- •Treatment with more than one prior line of treatment for advanced NSCLC
- •Treatment with an approved EGFR-TKI (e.g.,erlotinib, gefitinib, afatinib) within 8 days or approximately 5x half-life of the first dose of study treatment
- •Any investigational agents or other anticancer drugs from a previous treatment regimen or clinical study within 14 days of the first dose of study treatment
- •Previous treatment with Osimertinib, or a 3rd generation EGFR TKI
- •For subjects who cross-over to Osimertinib:
- •Once subjects on the platinum-based doublet chemotherapy arm are determined to have objective radiological progression according to RECIST 1.1 by the investigator and confirmed by independent central imaging review.
- •At least 14 days since last dose of platinum-based doublet chemotherapy
研究组 & 干预措施
Osimertinib
Osimertinib 80 mg, orally, once daily
干预措施: Chemotherapy (Drug)
Osimertinib
Osimertinib 80 mg, orally, once daily
干预措施: Cross-over to Osimertinib (Drug)
Platinum-based doublet chemotherapy
pemetrexed 500mg/m2 + carboplatin AUC5 or pemetrexed 500mg/m2 + cisplatin 75mg/m2
干预措施: Chemotherapy (Drug)
结局指标
主要结局
Progression Free Survival (PFS) by Investigator Assessment
时间窗: RECIST tumour assessments every 6 weeks from randomisation until objective disease progression up to 19 months (at the time of the primary PFS analysis).
Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT: Progressive Disease (PD): \>= 20% increase in the sum of diameters of TLs and an absolute increase in sum of diameters of \>=5mm (compared to the previous minimum sum) or progression of NTLs or a new lesion. PFS is the time from date of randomisation until the date of PD (by investigator assessment) or death (by any cause in the absence of progression) regardless of whether the patient withdrew from randomised therapy or received another anti-cancer therapy prior to progression. Patients who had not progressed or died at the time of analysis were censored at the time of the latest date of assessment from their last evaluable RECIST 1.1 assessment.
次要结局
- Duration of Response (DoR) by Investigator Assessment(RECIST tumour assessments every 6 weeks from randomisation until objective disease progression up to 19 months (at the time of the primary PFS analysis).)
- Secondary: Overall Survival (OS)(From date of randomization until time of final OS analysis, a median follow-up of 43 months)
- Objective Response Rate (ORR) by Investigator Assessment(RECIST tumour assessments every 6 weeks from randomisation until objective disease progression up to 19 months (at the time of the primary PFS analysis).)
- Tumour Shrinkage by Investigator Assessment(RECIST tumour assessments every 6 weeks from randomisation until objective disease progression up to 19 months (at the time of the primary PFS analysis).)
- Disease Control Rate (DCR) by Investigator Assessment(RECIST tumour assessments every 6 weeks from randomisation until objective disease progression up to 19 months (at the time of the primary PFS analysis).)