A Phase III, Open Label, Randomised, Multi-centre, International Study of MEDI4736, Given as Monotherapy or in Combination With Tremelimumab Determined by PD-L1 Expression Versus Standard of Care in Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer (Stage IIIB-IV) Who Have Received at Least Two Prior Systemic Treatment Regimens Including One Platinum Based Chemotherapy Regimen and Do Not Have Known EGFR TK Activating Mutations or ALK Rearrangements (ARCTIC).
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 597
- 试验地点
- 1
- 主要终点
- Overall Survival (OS)
研究概览
简要总结
This study is a Phase III, randomised, open label, multi-centre study assessing the efficacy and safety of MEDI4736 (durvalumab) versus Standard of Care in NSCLC patients with PD-L1 positive tumours and the combination of MEDI4736 (durvalumab) plus tremelimumab (MEDI4736+treme) versus Standard of Care in NSCLC patients with PD-L1-negative tumours in the treatment of male and female patients with locally advanced or metastatic NSCLC (Stage IIIB-IV), who have received at least 2 prior systemic treatment regimens including 1 platinum-based chemotherapy regimen for NSCLC. Patients with known EGFR (Epidermal growth factor receptor) tyrosine kinase (TK) activating mutations and anaplastic lymphoma kinase (ALK) rearrangements are not eligible for the study (prospective testing is not planned within this study). The Standard of Care options are: an EGFR tyrosine kinase inhibitor (erlotinib [TARCEVA®]), gemcitabine or vinorelbine (NAVELBINE®)
详细描述
The study has an umbrella design with 2 sub-studies: sub-study A (randomizing patients with PD-L1 positive tumours 1:1 into MEDI4736 (durvalumab) vs. Standard of Care) and sub-study B (randomizing patients with PD-L1 negative tumours 2:3:1:2 into MEDI4736 (durvalumab) vs. MEDI4736 (durvalumab) plus tremelimumab vs. tremelimumab vs. Standard of Care. The two substudies may have different durations of recruitment periods due to differences in patient population (PD-L1 expression). They may not run concurrently with start and completion of recruitment potentially occurring at different time points.
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
- •Aged at least 18 years
- •Documented evidence of NSCLC (Stage IIIB/ IV disease)
- •Disease progression or recurrence after both a platinum-based chemotherapy regimen and at least 1 additional regimen for treatment of NSCLC
- •World Health Organization (WHO) Performance Status of 0 or 1
- •Estimated life expectancy more than 12 weeks
排除标准
- •Prior exposure to any anti-PD-1 or anti-PD-L1 antibody or anti-CTLA4
- •Brain metastases or spinal cord compression unless asymptomatic, treated and stable (not requiring steroids)
- •Active or prior documented autoimmune disease within the past 2 years
- •Evidence of severe or uncontrolled systemic disease, including active bleeding diatheses or active infections including hepatitis B, C and HIV
- •Any unresolved toxicity CTCAE (Common Terminology Criteria of Adverse Events) >Grade 2 from previous anti-cancer therapy
- •Known EGFR TK activating mutations or ALK rearrangements
- •Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE >Grade 1
- •Active or prior documented inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis)
研究组 & 干预措施
MEDI4736 (durvalumab) monotherapy in Sub-study A
MEDI4736 (durvalumab) by intravenous infusion. Sub-study A for patients with PD-L1 positive tumors.
干预措施: MEDI4736 (durvalumab) (Drug)
Standard of Care in Sub-study A
Investigator choice from Vinorelbine, Gemcitabine and Erlotinib. Sub-study A for patients with PD-L1 positive tumors.
干预措施: Vinorelbine (Drug)
Standard of Care in Sub-study A
Investigator choice from Vinorelbine, Gemcitabine and Erlotinib. Sub-study A for patients with PD-L1 positive tumors.
干预措施: Gemcitabine (Drug)
Standard of Care in Sub-study A
Investigator choice from Vinorelbine, Gemcitabine and Erlotinib. Sub-study A for patients with PD-L1 positive tumors.
干预措施: Erlotinib (Drug)
MEDI4736 (durvalumab) + tremelimumab in Sub-study B
MEDI4736 (durvalumab) by intravenous infusion and tremelimumab by intravenous infusion. Sub-study B for patients with PD-L1 negative tumors.
干预措施: MEDI4736 (durvalumab) in combination with tremelimumab (anti-CTLA4) (Drug)
Standard of Care in Sub-study B
Investigator choice from Vinorelbine, Gemcitabine and Erlotinib. Sub-study B for patients with PD-L1 negative tumors.
干预措施: Vinorelbine (Drug)
Standard of Care in Sub-study B
Investigator choice from Vinorelbine, Gemcitabine and Erlotinib. Sub-study B for patients with PD-L1 negative tumors.
干预措施: Gemcitabine (Drug)
Standard of Care in Sub-study B
Investigator choice from Vinorelbine, Gemcitabine and Erlotinib. Sub-study B for patients with PD-L1 negative tumors.
干预措施: Erlotinib (Drug)
MEDI4736 (durvalumab) monotherapy in Sub-study B
MEDI4736 (durvalumab) by intravenous infusion. Sub-study B for patients with PD-L1 negative tumors.
干预措施: MEDI4736 (durvalumab) (Drug)
tremelimumab in Sub-study B
tremelimumab by intravenous infusion. Sub-study B for patients with PD-L1 negative tumors.
干预措施: tremelimumab (anti-CTLA4) (Drug)
结局指标
主要结局
Overall Survival (OS)
时间窗: From randomization (Day 1) until death due to any cause, approximately 36 months
The OS was defined as the time from the date of randomization until death due to any cause.
Progression-Free Survival (PFS)
时间窗: Tumour scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression. Assessed up to a maximum of approximately 3 years.
The PFS was defined as the time from the date of randomization until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the participant withdrew from randomized therapy or received another anti-cancer therapy prior to progression. The PFS was determined by Investigator assessments according to response evaluation criteria in solid tumours (RECIST) version 1.1. PD was defined as at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 millimeter (mm) or progression of non-target lesions or the appearance of a new lesion
次要结局
- Percentage of Participants Alive and Progression Free at 12 Months (APF12)(Tumour scans performed at baseline then every ~8 weeks up to 12 months.)
- OS, Contribution of the Components Analysis of Sub-study B(From randomization (Day 1) until death due to any cause, approximately 36 months)
- Percentage of Participants Alive at 12 Months (OS12)(From randomization (Day 1) up to 12 months)
- PFS, Contribution of the Components Analysis of Sub-study B(Tumour scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression. Assessed up to a maximum of approximately 3 years.)
- Objective Response Rate (ORR)(Tumour scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression. Assessed up to a maximum of approximately 3 years.)
- Duration of Response (DoR)(Tumour scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression. Assessed up to a maximum of approximately 3 years.)
- Percentage of Participants Alive and Progression Free at 6 Months (APF6)(Tumour scans performed at baseline then every ~8 weeks up to 6 months)
- Time From Randomisation to Second Progression (PFS2) of Sub-study B(Tumour scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~12 weeks thereafter until first progression. Disease then assessed per local practice until 2nd progression. Assessed up to a maximum of approximately 3 years.)