An Open-Label, Randomized, Phase 3 Trial of Nivolumab Versus Investigator's Choice Chemotherapy as First-Line Therapy for Stage IV or Recurrent PD-L1+ Non-Small Cell Lung Cancer
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 541
- 试验地点
- 141
- 主要终点
- Progression-Free Survival in Participants With PD-L1 Expression >= 5%
研究概览
简要总结
The purpose of this study is to show that Nivolumab will improve progression free survival in subjects with strongly Stage IV or Recurrent PD-L1+ non-small cell lung cancer when compared to chemotherapy
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤ 1
- •Histologically confirmed Stage IV, or Recurrent NSCLC with no prior systemic anticancer therapy
- •Measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) per response evaluation criteria in solid tumors version (RECIST) 1.1 criteria
- •PD-L1+ on immunohistochemistry testing performed by central lab
- •Men and women, ages ≥ 18 years of age
排除标准
- •Known epidermal growth factor receptor (EGFR) mutations which are sensitive to available targeted inhibitor therapy
- •Known anaplastic lymphoma kinase (ALK) translocations
- •Untreated central nervous system (CNS) metastases
- •Previous malignancies
- •Active, known or suspected autoimmune disease
研究组 & 干预措施
Arm A: Nivolumab subjects
Nivolumab solution for Injection 3 mg/kg Intravenous every 2 weeks until disease progression, discontinuation due to unacceptable toxicity, withdrawal of consent or study closure
干预措施: Nivolumab (Biological)
Arm B: Investigator's Choice Chemotherapy
Investigator's Choice Chemotherapy administered in 3-week cycles up to a maximum of 6 cycles of Intravenous injection until disease progression, unacceptable toxicity or completion of the 6 cycles, whichever comes first
Squamous subjects:
- Gemcitabine 1250 mg/mg(2) administered on Day 1 and Day 8 with Cisplatin 75 mg/m(2) administered on Day 1 of each cycle; or
- Gemcitabine 1000 mg/mg(2) administered on Day 1 and Day 8 with Carboplatin (AUC 5) administered on Day 1 of each cycle; or
- Paclitaxel 200 mg/m(2) with Carboplatin (AUC 6) administered on Day 1 of each cycle
Non-Squamous subjects:
- Pemetrexed 500 mg/m(2) with Cisplatin 75 mg/m(2) administered on Day 1 of each cycle
- Pemetrexed 500 mg/m(2) Carboplatin (AUC 6) administered on Day 1 of each cycle
Optional crossover:
- Nivolumab solution for Injection 3 mg/kg Intravenous every 2 weeks until disease progression, discontinuation due to toxicity, withdrawal of consent or study closure
干预措施: Nivolumab (Biological)
Arm B: Investigator's Choice Chemotherapy
Investigator's Choice Chemotherapy administered in 3-week cycles up to a maximum of 6 cycles of Intravenous injection until disease progression, unacceptable toxicity or completion of the 6 cycles, whichever comes first
Squamous subjects:
- Gemcitabine 1250 mg/mg(2) administered on Day 1 and Day 8 with Cisplatin 75 mg/m(2) administered on Day 1 of each cycle; or
- Gemcitabine 1000 mg/mg(2) administered on Day 1 and Day 8 with Carboplatin (AUC 5) administered on Day 1 of each cycle; or
- Paclitaxel 200 mg/m(2) with Carboplatin (AUC 6) administered on Day 1 of each cycle
Non-Squamous subjects:
- Pemetrexed 500 mg/m(2) with Cisplatin 75 mg/m(2) administered on Day 1 of each cycle
- Pemetrexed 500 mg/m(2) Carboplatin (AUC 6) administered on Day 1 of each cycle
Optional crossover:
- Nivolumab solution for Injection 3 mg/kg Intravenous every 2 weeks until disease progression, discontinuation due to toxicity, withdrawal of consent or study closure
干预措施: Gemcitabine (Drug)
Arm B: Investigator's Choice Chemotherapy
Investigator's Choice Chemotherapy administered in 3-week cycles up to a maximum of 6 cycles of Intravenous injection until disease progression, unacceptable toxicity or completion of the 6 cycles, whichever comes first
Squamous subjects:
- Gemcitabine 1250 mg/mg(2) administered on Day 1 and Day 8 with Cisplatin 75 mg/m(2) administered on Day 1 of each cycle; or
- Gemcitabine 1000 mg/mg(2) administered on Day 1 and Day 8 with Carboplatin (AUC 5) administered on Day 1 of each cycle; or
- Paclitaxel 200 mg/m(2) with Carboplatin (AUC 6) administered on Day 1 of each cycle
Non-Squamous subjects:
- Pemetrexed 500 mg/m(2) with Cisplatin 75 mg/m(2) administered on Day 1 of each cycle
- Pemetrexed 500 mg/m(2) Carboplatin (AUC 6) administered on Day 1 of each cycle
Optional crossover:
- Nivolumab solution for Injection 3 mg/kg Intravenous every 2 weeks until disease progression, discontinuation due to toxicity, withdrawal of consent or study closure
干预措施: Cisplatin (Drug)
Arm B: Investigator's Choice Chemotherapy
Investigator's Choice Chemotherapy administered in 3-week cycles up to a maximum of 6 cycles of Intravenous injection until disease progression, unacceptable toxicity or completion of the 6 cycles, whichever comes first
Squamous subjects:
- Gemcitabine 1250 mg/mg(2) administered on Day 1 and Day 8 with Cisplatin 75 mg/m(2) administered on Day 1 of each cycle; or
- Gemcitabine 1000 mg/mg(2) administered on Day 1 and Day 8 with Carboplatin (AUC 5) administered on Day 1 of each cycle; or
- Paclitaxel 200 mg/m(2) with Carboplatin (AUC 6) administered on Day 1 of each cycle
Non-Squamous subjects:
- Pemetrexed 500 mg/m(2) with Cisplatin 75 mg/m(2) administered on Day 1 of each cycle
- Pemetrexed 500 mg/m(2) Carboplatin (AUC 6) administered on Day 1 of each cycle
Optional crossover:
- Nivolumab solution for Injection 3 mg/kg Intravenous every 2 weeks until disease progression, discontinuation due to toxicity, withdrawal of consent or study closure
干预措施: Carboplatin (Drug)
Arm B: Investigator's Choice Chemotherapy
Investigator's Choice Chemotherapy administered in 3-week cycles up to a maximum of 6 cycles of Intravenous injection until disease progression, unacceptable toxicity or completion of the 6 cycles, whichever comes first
Squamous subjects:
- Gemcitabine 1250 mg/mg(2) administered on Day 1 and Day 8 with Cisplatin 75 mg/m(2) administered on Day 1 of each cycle; or
- Gemcitabine 1000 mg/mg(2) administered on Day 1 and Day 8 with Carboplatin (AUC 5) administered on Day 1 of each cycle; or
- Paclitaxel 200 mg/m(2) with Carboplatin (AUC 6) administered on Day 1 of each cycle
Non-Squamous subjects:
- Pemetrexed 500 mg/m(2) with Cisplatin 75 mg/m(2) administered on Day 1 of each cycle
- Pemetrexed 500 mg/m(2) Carboplatin (AUC 6) administered on Day 1 of each cycle
Optional crossover:
- Nivolumab solution for Injection 3 mg/kg Intravenous every 2 weeks until disease progression, discontinuation due to toxicity, withdrawal of consent or study closure
干预措施: Paclitaxel (Drug)
Arm B: Investigator's Choice Chemotherapy
Investigator's Choice Chemotherapy administered in 3-week cycles up to a maximum of 6 cycles of Intravenous injection until disease progression, unacceptable toxicity or completion of the 6 cycles, whichever comes first
Squamous subjects:
- Gemcitabine 1250 mg/mg(2) administered on Day 1 and Day 8 with Cisplatin 75 mg/m(2) administered on Day 1 of each cycle; or
- Gemcitabine 1000 mg/mg(2) administered on Day 1 and Day 8 with Carboplatin (AUC 5) administered on Day 1 of each cycle; or
- Paclitaxel 200 mg/m(2) with Carboplatin (AUC 6) administered on Day 1 of each cycle
Non-Squamous subjects:
- Pemetrexed 500 mg/m(2) with Cisplatin 75 mg/m(2) administered on Day 1 of each cycle
- Pemetrexed 500 mg/m(2) Carboplatin (AUC 6) administered on Day 1 of each cycle
Optional crossover:
- Nivolumab solution for Injection 3 mg/kg Intravenous every 2 weeks until disease progression, discontinuation due to toxicity, withdrawal of consent or study closure
干预措施: Pemetrexed (Drug)
结局指标
主要结局
Progression-Free Survival in Participants With PD-L1 Expression >= 5%
时间窗: From date of randomization until date of documented tumor progression (assessed up to August 2016, approximately 28 months)
Progression-Free Survival (PFS) was defined as the time between the date of randomization and the first date of documented tumor progression, as determined by the Independent Radiology Review Committee (IRRC) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, or death due to any cause, whichever occurs first. Participants who die without a reported progression were considered to have progressed on the date of their death. Participants who did not progress or die were censored on the date of their last evaluable tumor assessment. Participants who did not have any on-study tumor assessments and did not die were censored on the day they were randomized. Participants who received subsequent anti-cancer therapy prior to documented progression were censored at the last evaluable tumor assessment prior to the initiation of new therapy.
次要结局
- Progression-Free Survival in All Randomized Participants(From date of randomization until date of documented tumor progression (assessed up to August 2016, approximately 28 months))
- Overall Survival in Participants With PD-L1 Expression >= 5%(From date of randomization to date of death (up to approximately 89 months))
- Overall Survival in All Randomized Participants(From date of randomization to date of death (up to approximately 89 months))
- Objective Response Rate (ORR) in Participants With PD-L1 Expression >= 5%(From date of randomization until date of documented tumor progression or subsequent anti-cancer therapy, whichever occurs first (assessed up to August 2016, approximately 28 months))
- Disease-related Symptom Improvement Rate by Week 12(From date of randomization to week 12)