NCT03521154进行中（未招募）3 期
A Phase III, Randomized, Double-blind, Placebo-controlled, Multicenter, International Study of Osimertinib as Maintenance Therapy in Patients With Locally Advanced, Unresectable EGFR Mutation-positive Non-Small Cell Lung Cancer (Stage III) Whose Disease Has Not Progressed Following Definitive Platinum-based Chemoradiation Therapy (LAURA).
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- AstraZeneca
- 入组人数
- 216
- 试验地点
- 119
- 主要终点
- Progression-free Survival (PFS) by Blinded Independent Central Review (BICR)
研究概览
简要总结
A global study to assess the efficacy and safety of osimertinib following chemoradiation in patients with stage III unresectable Epidermal Growth Factor Receptor Mutation Positive non-small cell lung cancer
详细描述
This is a phase 3 double-blind, randomized, placebo-controlled, study to assess the efficacy and safety of osimertinib following chemoradiation in patients with stage III unresectable EGFR mutation-positive NSCLC, including the most common EGFR sensitising mutations (Ex19Del and L858R), either alone or in combination with other EGFR mutations. Chemoradiation may have been given either given concurrently or sequentially. Patients whose disease has not progressed following chemoradiation will be randomised within 6 weeks of completion of chemoradiation to receive osimertinib or placebo in a 2:1 ratio, and treatment will be continued until disease progression, unacceptable toxicity or other discontinuation criteria are met. After progression, patients can be unblinded and may receive open-label osimertinib. After the final OS analysis, the study blind will be broken and patients still receiving open-label osimertinib will be supplied with open-label osimertinib by AstraZeneca for as long as their treating physician considers they are deriving clinical benefit.
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
- Double (Participant, Investigator)
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
- •Male or female aged at least 18 years.
- •Patients with histologically documented NSCLC of predominantly non-squamous Pathology who present with locally advanced, unresectable (Stage III) disease (according to Version 8 of the International Association for the Study of Lung Cancer [IASLC] Staging Manual in Thoracic Oncology).
- •The tumor harbours one of the two common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R), either alone or in combination with other EGFR mutations, assessed by cobas® EGFR Mutation Test v2 (Roche Diagnostics) or FoundationOne® test in a CLIA certified (USA sites) or an accredited local laboratory (sites outside of the USA) or by central testing (cobas® v2 only).
- •Patients must have received either concurrent chemoradiation or sequential chemoradiation including at least 2 cycles of platinum based chemotherapy and a total dose of radiation of 60 Gy ±10% (54 to 66 Gy).
- •Chemoradiation must be completed ≤6 weeks prior to randomization.
- •Patients must not have had disease progression during or following definitive platinum-based, chemoradiation therapy.
- •World Health Organization (WHO) performance status of 0 or
- •Life expectancy >12 weeks at Day
- •Female patients who are not abstinent (in line with the preferred and usual lifestyle choice) must be using adequate contraceptive measures, must not be breast feeding, and must have a negative pregnancy test prior to first dose of study drug; or female patients must have an evidence of non-childbearing potential.
排除标准
- •Mixed small cell and non-small cell lung cancer histology
- •History of interstitial lung disease (ILD) prior to chemoradiation
- •Symptomatic pneumonitis following chemoradiation
- •Any unresolved toxicity Common Terminology Criteria for Adverse Events (CTCAE) > Grade 2 from the prior chemoradiation therapy
- •Any of the following cardiac criteria:
- •Mean resting corrected QT interval (QTc) >470 msec, obtained from 3 ECGs
- •Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG
- •Patient with any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in first-degree relatives or any concomitant medication known to prolong the QT interval and cause Torsades de Pointes
- •Inadequate bone marrow reserve or organ function
- •History of other malignancies, except: adequately treated non-melanoma skin cancer or lentigo maligna , curatively treated in-situ cancer, or other solid tumors curatively treated with no evidence of disease for > 5 years following the end of treatment and which, in the opinion of the treating physician, do not have a substantial risk of recurrence of the prior malignancy.
- •Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses; or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV).
- •Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption of osimertinib
- •Prior treatment with any prior chemotherapy, radiation therapy, immunotherapy or investigational agents for NSCLC outside of that received in the definitive setting for Stage III disease (chemotherapy and radiotherapy in SCRT and CCRT regimens is allowed for treatment of Stage III disease).
- •Prior treatment with EGFR-TKI therapy
- •Major surgery as defined by the investigator within 4 weeks of the first dose of study drug.
- •Patients currently receiving (unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be strong inducers of CYP3A4 (at least 3 weeks prior to receiving the first dose of study drug).
- •Contraindication to MRI, including but not limited to, claustrophobia, pace makers, metal implants, intracranial surgical clips and metal foreign bodies
研究组 & 干预措施
Osimertinib
Experimental
Osimertinib (80mg or 40mg orally, once daily), in accordance with the randomization schedule.
干预措施: Osimertinib 80mg/40mg (Drug)
Placebo Osimertinib
Placebo Comparator
Matching placebo for Osimertinib (80mg or 40mg orally, once daily), in accordance with the randomization schedule
干预措施: Placebo Osimertinib 80mg/40mg (Drug)
结局指标
主要结局
Progression-free Survival (PFS) by Blinded Independent Central Review (BICR)
时间窗: Every 8 weeks for first 48 weeks, then every 12 weeks until BICR-confirmed radiological disease progression. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months
Time from randomisation until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from randomised therapy or receives another anti-cancer therapy prior to progression, based on BICR assessment according to RECIST v1.1
次要结局
- Number of Participants With Progression-free Survival (PFS) Events in Patients With EGFR Ex19del or L858R Mutation(Every 8 weeks for first 48 weeks, then every 12 weeks until BICR-confirmed radiological disease progression. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months)
- Number of Participants With Progression-free Survival (PFS) Events in Patients With EGFR Mutations Ex19del or L858R Detectable in Plasma-derived ctDNA(Every 8 weeks for first 48 weeks, then every 12 weeks until BICR-confirmed radiological disease progression. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months)
- Central Nervous System (CNS) Progression-free Survival (PFS) by Blinded Independent Central Review (BICR)(Every 8 weeks for first 48 weeks, then every 12 weeks until BICR-confirmed radiological disease progression. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months)
- Overall Survival (Count)(Date of randomisation to date of death by any cause. Assessed up to a maximum of approximately 63 months)
- Overall Survival (Duration)(Date of randomisation to date of death by any cause. Assessed up to a maximum of approximately 63 months)
- Objective Response Rate by Blinded Independent Central Review (BICR)(Every 8 weeks for first 48 weeks, then every 12 weeks until radiological disease progression. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months)
- Duration of Response, Unconfirmed by Blinded Independent Central Review (BICR)(Every 8 weeks for first 48 weeks, then every 12 weeks until radiological disease progression. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months)
- Disease Control Rate by Blinded Independent Central Review (BICR)(Every 8 weeks for first 48 weeks, then every 12 weeks until BICR-confirmed radiological disease progression. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months)
- Tumour Shrinkage by Blinded Independent Central Review (BICR)(Every 8 weeks for first 48 weeks, then every 12 weeks until BICR-confirmed radiological disease progression. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months)
- Proportion With Tumour Shrinkage by Blinded Independent Central Review (BICR)(Every 8 weeks for first 48 weeks, then every 12 weeks until BICR-confirmed radiological disease progression. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months)
- Time to Death or Distant Metastases by Blinded Independent Central Review (BICR)(Time from randomisation to the date of distant metastases or death. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months)
- Time to Study Treatment Discontinuation(Time from randomisation to the earlier of the date of study treatment discontinuation or death. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months)
- Time to First Subsequent Treatment(Time from randomisation to the start of first subsequent anti-cancer therapy or death. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months)
- Time to Second Subsequent Treatment(Time from randomisation to the start of second subsequent anti-cancer therapy or death. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months)
- Second Progression-free Survival (PFS2)(Every 8 weeks for first 48 weeks, then every 12 weeks. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months)
研究者
研究点 (119)
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相关资讯
Osimertinib Recommended for EU Approval in Locally Advanced EGFR-Mutated NSCLC After Chemoradiation- The European Medicines Agency's CHMP recommended osimertinib for unresectable EGFR-mutated NSCLC after platinum-based chemoradiation.
- The recommendation is based on the Phase 3 LAURA trial, which showed an 84% reduction in disease progression or death with osimertinib versus placebo.
- Median progression-free survival was 39.1 months with osimertinib compared to 5.6 months with placebo in the LAURA trial.
- Osimertinib has demonstrated benefit across all stages of EGFR-mutated lung cancer, representing a pivotal step in transforming care.last yearPrecision Medicine Advances in Oncology: Targeted Therapies Show Promise in Multiple Cancers- Lorlatinib demonstrates a 60% 5-year progression-free survival rate in ALK-positive NSCLC, significantly surpassing crizotinib's 8%.
- Osimertinib as adjuvant therapy post-chemoradiation shows 74% of patients progression-free at 12 months in EGFR-mutated stage III NSCLC, compared to 22% with placebo.
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- Ribociclib (Kisqali) gained approval for early-stage breast cancer, expanding treatment options for this disease and showing improved invasive disease-free survival.
- Pembrolizumab (Keytruda) in combination with chemotherapy was approved for unresectable advanced or metastatic malignant pleural mesothelioma, improving overall survival.
- Isatuximab (Sarclisa) plus bortezomib, lenalidomide, and dexamethasone was approved for transplant-ineligible, newly diagnosed multiple myeloma patients.last yearOsimertinib's Expanding Role in EGFR-Mutated NSCLC Explored at ASCO 2024- The phase 3 LAURA trial demonstrated that osimertinib significantly improved progression-free survival in patients with stage III, EGFR-mutated NSCLC following chemoradiotherapy.
- Minimal residual disease (MRD) monitoring in the phase 3 ADAURA trial may influence future treatment timelines for EGFR-mutated NSCLC, according to experts.
- FLAURA2 trial results highlight the evolving role of osimertinib in advanced EGFR-mutated NSCLC, particularly concerning patients with brain metastases.
- Experts discussed the potential impact of liquid biopsy data on treatment decisions for patients with EGFR-mutated NSCLC.2 years agoRecent Advances in Oncology: FDA Approvals, Promising Therapies, and Evolving Treatment Strategies- The FDA approved inavolisib plus palbociclib/fulvestrant for endocrine-resistant, PIK3CA-mutated, HR+/HER2- advanced breast cancer, significantly improving progression-free survival.
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