NCT03003962进行中（未招募）3 期
A Phase III Randomized, Open-Label, Multi-Center Study of Durvalumab (MEDI4736) Versus Standard of Care (SoC) Platinum-Based Chemotherapy as First Line Treatment in Patients With PD-L1-High Expression Advanced Non Small-Cell Lung Cancer
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
- 669
- 试验地点
- 93
- 主要终点
- Overall Survival (OS)
研究概览
简要总结
This is a randomized, open-label, multi-center Phase III study to determine the efficacy and safety of durvalumab versus platinum-based SoC chemotherapy in the first-line treatment of advanced NSCLC in patients who are epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) wild-type and with PD-L1 high expression (PEARL)
详细描述
Patients with stage IV NSCLC will be randomized in a 1:1 ratio to 2 treatment arms (durvalumab or SOC therapy). The dual primary objectives of this study are to assess the efficacy of durvalumab versus SoC in terms of OS (Overall Survival) in all randomized patients and in patients who are at low risk of EM (early mortality)
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 Stage IV NSCLC
- •No sensitizing EGFR mutation and ALK rearrangement
- •PD-L1 high expression
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
排除标准
- •Prior chemotherapy or any other systemic therapy for advanced NSCLC
- •Prior exposure to immune-mediated therapy, including, but not limited to, other anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), anti-programmed cell death1 (PD-1), anti-programmed cell death ligand 1 (PD-L1), or anti PD-L2 antibodies, excluding therapeutic anticancer vaccines
- •Brain metastases or spinal cord compression unless the patient is stable and off steroids for at least 14 days prior to start of study treatment
- •Mixed small-cell lung cancer and NSCLC histology, sarcomatoid variant
- •Active or prior documented autoimmune or inflammatory disorders (e.g., colitis or Crohn's disease]
研究组 & 干预措施
Arm 1: Durvalumab
Experimental
Anti-PD-L1 monoclonal Antibody monotherapy
干预措施: Durvalumab (MEDI4736) (Drug)
Arm 2: Standard of Care
Active Comparator
Standard of Care Platinum-Based chemotherapy
干预措施: Paclitaxel + carboplatin (Drug)
Arm 2: Standard of Care
Active Comparator
Standard of Care Platinum-Based chemotherapy
干预措施: Gemcitabine + cisplatin (Drug)
Arm 2: Standard of Care
Active Comparator
Standard of Care Platinum-Based chemotherapy
干预措施: Gemcitabine + carboplatin (Drug)
Arm 2: Standard of Care
Active Comparator
Standard of Care Platinum-Based chemotherapy
干预措施: Pemetrexed + cisplatin (Drug)
Arm 2: Standard of Care
Active Comparator
Standard of Care Platinum-Based chemotherapy
干预措施: Pemetrexed + carboplatin (Drug)
结局指标
主要结局
Overall Survival (OS)
时间窗: From date of randomization until death due to any cause. Assessed up to a maximum of approximately 69 months [data cut-off (DCO) 27 October 2022]
OS is defined as the time from the date of randomization until death due to any cause (date of death or censoring-date of randomization + 1). Any participant not known to have died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive.
OS in Participants With LREM
时间窗: From date of randomization until death due to any cause. Assessed up to a maximum of approximately 69 months (DCO 27 October 2022)
OS is defined as the time from the date of randomization until death due to any cause (date of death or censoring-date of randomization + 1). Any participant not known to have died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive.
次要结局
- DoR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >=50% Analysis Set(Tumor assessments (per RECIST 1.1) every 6 weeks for the first 48 weeks relative to the date of randomization and then every 8 weeks thereafter until confirmed objective disease progression (up to a maximum of approximately 69 months))
- OS in PD-L1 TC >= 50% LREM Analysis Set(From date of randomization until death due to any cause. Assessed up to a maximum of approximately 69 months (DCO 27 October 2022))
- ORR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >= 50% LREM Analysis Set(Tumor assessments (per RECIST 1.1) every 6 weeks for the first 48 weeks relative to the date of randomization and then every 8 weeks thereafter until confirmed objective disease progression (up to a maximum of approximately 69 months))
- DoR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >=25% LREM Analysis Set(Tumor assessments (per RECIST 1.1) every 6 weeks for the first 48 weeks relative to the date of randomization and then every 8 weeks thereafter until confirmed objective disease progression (up to a maximum of approximately 69 months))
- APF12 in PD-L1 TC >= 25% LREM Analysis Set(From date of randomization until 12 months)
- APF12 in PD-L1 TC >= 50% LREM Analysis Set(From date of randomization until 12 months)
- OS at 18 Months(From date of randomization till 18 months.)
- OS at 18 Months in PD-L1 TC > = 25% LREM Analysis Set(From date of randomization till 18 months)
- OS at 18 Months in PD-L1 TC >= 50% LREM Analysis Set(From date of randomization till 18 months)
- OS in PD-L1 TC >= 50% Analysis Set(From date of randomization until death due to any cause. Assessed up to a maximum of approximately 69 months (DCO 27 October 2022))
- PFS Based on Investigator Assessment According to RECIST 1.1 in PD-L1 TC >= 50% Analysis Set(Tumor assessments (per RECIST 1.1) every 6 weeks for the first 48 weeks relative to the date of randomization and then every 8 weeks thereafter until confirmed objective disease progression (up to a maximum of approximately 69 months))
- PFS Based on Investigator Assessment According to RECIST 1.1 in PD-L1 TC >= 50% LREM Analysis Set(Tumor assessments (per RECIST 1.1) every 6 weeks for the first 48 weeks relative to the date of randomization and then every 8 weeks thereafter until confirmed objective disease progression (up to a maximum of approximately 69 months))
- ORR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >= 25% LREM Analysis Set(Tumor assessments (per RECIST 1.1) every 6 weeks for the first 48 weeks relative to the date of randomization and then every 8 weeks thereafter until confirmed objective disease progression (up to a maximum of approximately 69 months))
- ORR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >= 50% Analysis Set(Tumor assessments (per RECIST 1.1) every 6 weeks for the first 48 weeks relative to the date of randomization and then every 8 weeks thereafter until confirmed objective disease progression (up to a maximum of approximately 69 months))
- Duration of Response (DoR) as Per RECIST 1.1 Using Investigator Assessment(Tumor assessments (per RECIST 1.1) every 6 weeks for the first 48 weeks relative to the date of randomization and then every 8 weeks thereafter until confirmed objective disease progression (up to a maximum of approximately 69 months))
- DoR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >=50% LREM Analysis Set(Tumor assessments (per RECIST 1.1) every 6 weeks for the first 48 weeks relative to the date of randomization and then every 8 weeks thereafter until confirmed objective disease progression (up to a maximum of approximately 69 months))
- Progression Free Survival (PFS) Based on Investigator Assessment According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)(Tumor assessments (per RECIST 1.1) every 6 weeks for the first 48 weeks relative to the date of randomization and then every 8 weeks thereafter until confirmed objective disease progression (up to a maximum of approximately 69 months DCO 27 October 2022))
- PFS Based on Investigator Assessment According to RECIST 1.1 in LREM Analysis Set(Tumor assessments (per RECIST 1.1) every 6 weeks for the first 48 weeks relative to the date of randomization and then every 8 weeks thereafter until confirmed objective disease progression (up to a maximum of approximately 69 months))
- Objective Response Rate (ORR) as Per RECIST 1.1 Using Investigator Assessment(Tumor assessments (per RECIST 1.1) every 6 weeks for the first 48 weeks relative to the date of randomization and then every 8 weeks thereafter until confirmed objective disease progression (up to a maximum of approximately 69 months))
- Time From Randomization to Second Progression (PFS2)(Tumor assessments (per RECIST 1.1) until confirmed objective disease progression. Disease then assessed as per local practice until 2nd progression or death (up to a maximum of approximately 69 months))
- Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status(From Baseline and until follow-up period of 57 months)
- PFS2 in PD-L1 TC >= 25% LREM Analysis Set(Tumor assessments (per RECIST 1.1) until confirmed objective disease progression. Disease then assessed as per local practice until 2nd progression or death (up to a maximum of approximately 69 months))
- PFS2 in PD-L1 TC >= 50% LREM Analysis Set(Tumor assessments (per RECIST 1.1) until confirmed objective disease progression. Disease then assessed as per local practice until 2nd progression or death (up to a maximum of approximately 69 months))
- OS at 18 Months in PD-L1 TC >= 50% Analysis Set(From date of randomization till 18 months)
- Alive and Progression-Free at 12 Months (APF12)(From date of randomization until 12 months)
- APF12 in PD-L1 TC >= 50% Analysis Set(From date of randomization until 12 months)
- PFS2 in PD-L1 TC >= 50% Analysis Set(Tumor assessments (per RECIST 1.1) until confirmed objective disease progression. Disease then assessed as per local practice until 2nd progression or death (up to a maximum of approximately 69 months))
- OS at 24 Months(From date of randomization till 24 months)
- OS at 24 Months in PD-L1 TC >= 50% Analysis Set(From date of randomization till 24 months)
- OS at 24 Months in PD-L1 TC >= 50% LREM Analysis Set(From date of randomization till 24 months)
- Time to Deterioration of EORTC QLQ-C30(From randomization until date of first symptom deterioration that is confirmed, assessed up to a maximum of approximately 69 months (DCO 27 October 2022))
- Time to Deterioration of EORTC QLQ-LC13 in PD-L1 TC >= 25% LREM Analysis Set(From randomization until date of first symptom deterioration that is confirmed, assessed up to maximum of approximately 69 months (DCO 27 October 2022))
- Percentage of Participants With ADA Response to Durvalumab in LREM Analysis Set(Up to 24 weeks)
- OS at 24 Months in PD-L1 TC > = 25% LREM Analysis Set(From date of randomization till 24 months)
- Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) 30-Item Core Quality of Life Questionnaire Version 3 (QLQ-C30)(Baseline and 12 months)
- Change From Baseline in EORTC QLQ-C30 in PD-L1 TC >= 25% LREM Analysis Set(Baseline and 12 months)
- Time to Deterioration of EORTC QLQ-C30 in PD-L1 TC >= 25% LREM Analysis Set(From randomization until date of first symptom deterioration that is confirmed, assessed up to a maximum of approximately 69 months (DCO 27 October 2022))
- Change From Baseline in EORTC 13-Item Lung Cancer Quality of Life Questionnaire (QLQ-LC13)(Baseline and 12 months)
- Change From Baseline in EORTC QLQ-LC13 in PD-L1 TC >= 25% LREM Analysis Set(Baseline and 12 months)
- Number of Participants With ECOG Performance Status in PD-L1 TC >=25% LREM Analysis Set(From Baseline and until follow-up period of 57 months)
- Percentage of Participants With Antidrug Antibody (ADA) Response to Durvalumab(Up to 24 weeks)
- Time to Deterioration of EORTC QLQ-LC13(From randomization until date of first symptom deterioration that is confirmed, assessed up to maximum of approximately 69 months (DCO 27 October 2022))
研究者
研究点 (93)
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