Open-Label, Randomized Trial of Nivolumab (BMS-936558) Plus Pemetrexed/Platinum or Nivolumab Plus Ipilimumab (BMS-734016) vs Pemetrexed Plus Platinum in Stage IV or Recurrent Non-Small Cell Lung Cancer (NSCLC) Subjects With Epidermal Growth Factor Receptor (EGFR) Mutation Who Failed 1L or 2L EGFR Tyrosine Kinase Inhibitor Therapy
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 367
- 试验地点
- 51
- 主要终点
- Progression Free Survival (PFS) by Blinded Independent Centralized Review (BICR)
研究概览
简要总结
The main purpose of this study is to determine whether nivolumab + chemotherapy is effective as compared to chemotherapy in the treatment of patients with EGFR mutation, NSCLC who failed first line (1L) or second-line (2L) EGFR TKI therapy.
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
- •Confirmed stage IV or recurrent EGFR mutated NSCLC with disease progression on one or two prior lines of treatment with EGFR TKIs (allowed TKIs must be approved by the local health authority, including but not limited to erlotinib, gefitinib, afatinib, dacomitinib and osimertinib). In osimertinib treated subjects, T790 testing is not required.
- •No evidence of exon 20 T790M mutation obtained at progression on prior first- or second-generation EGFR TKI therapy. For participants who were treated with osimertinib, T790M testing is not required.
- •Measurable disease according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)
- •Available tumor sample for Programmed death-ligand 1 (PD-L1) immunohistochemical (IHC).
- •Participants are eligible if central nervous system (CNS) metastases are considered to be adequately controlled/treated before or during the screening period and participants are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to randomization. In addition, participants must be either off corticosteroids, or on a stable or decreasing dose of ≤10 mg daily prednisone (or equivalent) for at least 2 weeks prior to randomization). Participants with asymptomatic CNS metastasis are eligible.
- •Eastern Cooperative Group (ECOG) Performance Status 0-1
- •Life expectancy is at least 3 months
排除标准
- •Known EGFR mutation, T790M positive who failed 1L first- or second-generation TKI should receive osimertinib first as the standard of care (SOC). These participants are only eligible if they fail osimertinib as 2L.
- •who have progressed within 3 months of the first dose of 1L or 2L EGFR TKI.
- •Carcinomatous meningitis
- •Active, known or suspected autoimmune disease are excluded
- •ALK translocation
- •Known SCLC transformation
- •Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
- •Other protocol defined inclusion/exclusion criteria apply
研究组 & 干预措施
Nivolumab+Platinum doublet chemotherapy
干预措施: Nivolumab (Biological)
Nivolumab+Platinum doublet chemotherapy
干预措施: Pemetrexed (Drug)
Nivolumab+Platinum doublet chemotherapy
干预措施: Cisplatin (Drug)
Nivolumab+Platinum doublet chemotherapy
干预措施: Carboplatin (Drug)
Nivolumab + Ipilimumab
Enrollment is closed for this arm
干预措施: Nivolumab (Biological)
Nivolumab + Ipilimumab
Enrollment is closed for this arm
干预措施: Ipilimumab (Biological)
Platinum doublet chemotherapy
干预措施: Pemetrexed (Drug)
Platinum doublet chemotherapy
干预措施: Cisplatin (Drug)
Platinum doublet chemotherapy
干预措施: Carboplatin (Drug)
结局指标
主要结局
Progression Free Survival (PFS) by Blinded Independent Centralized Review (BICR)
时间窗: From randomization to the date of first documented tumor progression or death (approximately 58 months)
PFS is defined as the time between the date of randomization and the date of first documented tumor progression, as determined by BICR (per RECIST v1.1 criteria), or death due to any cause, whichever occurs first. Participants who died without reported progression will be considered to have progressed on the date of their death. Subsequent therapy was accounted for by censoring at the last evaluable tumor assessment on or prior to the date of subsequent therapy. Progression is the appearance of one or more new lesions. RECIST - "response evaluation criteria in solid tumors" is a standard system to measure tumor response to treatment. Based on Kaplan-Meier estimates
次要结局
- Duration of Response (DOR) by Blinded Independent Centralized Review (BICR)(From randomization to the date of first documented disease progression or death due to any cause (approximately 67 months))
- 12 Month Progression Free Survival Rates (PFSR) by Blinded Independent Centralized Review (BICR)(12 Months after first treatment dose)
- 9 Month Progression Free Survival Rates (PFSR) by Blinded Independent Centralized Review (BICR)(9 months after first treatment dose)
- Overall Survival (OS)(From randomization to the date of death due to any cause (up to approximately 67 months))
- Objective Response Rate (ORR) by Blinded Independent Centralized Review (BICR)(From randomization to the date of objectively documented progression, date of death, or the date of subsequent therapy (up to approximately 67 months))