A Study of Nivolumab in Combination With Ipilimumab (Part 1); and Nivolumab Plus Ipilimumab in Combination With Chemotherapy (Part 2) as First Line Therapy in Stage IV Non-Small Cell Lung Cancer (NSCLC)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 324
- 试验地点
- 32
- 主要终点
- Number of Participants With Adverse Events (AEs) - Part 2
研究概览
简要总结
The purpose of part 1 of this study is to determine the objective response rate (ORR) in stage IV NSCLC subjects treated with nivolumab in combination with ipilimumab as first line therapy.
The purpose of part 2 of this study is to determine the safety and tolerability of nivolumab and ipilimumab combined with a short course of chemotherapy in first line stage IV NSCLC.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •Men and Women ≥ 18 years of age
- •Diagnosed with stage IV Non-Small Cell Lung Cancer
- •Diagnosed with recurrent stage IIIB non-small cell lung cancer and failed previous concurrent chemoradiation with no further curative options.
排除标准
- •Subjects with untreated CNS metastases are excluded.
- •Subjects with carcinomatous meningitis
- •Subjects with an active, known or suspected autoimmune disease.
- •Subjects with a condition requiring systemic treatment with either corticosteroids ( > 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of first treatment.
- •Women who are pregnant, plan to become pregnant, and/or breastfeed during the study.
- •Other protocol defined inclusion/exclusion criteria apply
研究组 & 干预措施
Nivolumab+Ipilimumab
Part 1
Specified Dose on Specified Days
干预措施: Nivolumab (Biological)
Nivolumab+Ipilimumab
Part 1
Specified Dose on Specified Days
干预措施: Ipilimumab (Biological)
Nivolumab+Ipilimumab + 2 cycles Platinum Doublet Chemotherapy
Part 2
Specified Dose on Specified Days
干预措施: Nivolumab (Biological)
Nivolumab+Ipilimumab + 2 cycles Platinum Doublet Chemotherapy
Part 2
Specified Dose on Specified Days
干预措施: Ipilimumab (Biological)
Nivolumab+Ipilimumab + 2 cycles Platinum Doublet Chemotherapy
Part 2
Specified Dose on Specified Days
干预措施: Platinum Doublet Chemotherapy (Drug)
结局指标
主要结局
Number of Participants With Adverse Events (AEs) - Part 2
时间窗: Deaths are from first dose to database lock (Up to 24 months). AEs and SAEs are from first dose to 30 days post last dose
Number of participants with adverse events (AEs) including serious adverse events (SAEs) and deaths graded by Common Terminology Criteria for Adverse Events (CTCAE v4.0) to determine the safety and tolerability of Nivolumab and Ipilimumab combined with chemotherapy.
Number of Participants With Laboratory Abnormalities in Hepatic Tests - Part 2
时间窗: From first dose to 30 days post last dose
Number of participant with specific liver laboratory abnormalities graded by Common Terminology Criteria for Adverse Events (CTCAE v4.0) to determine the safety and tolerability of Nivolumab and Ipilimumab combined with chemotherapy.
Objective Response Rate (ORR) by PD-L1 Positive and Negative Levels - Part 1
时间窗: From first dose to database lock (Up to 18 months)
Objective response rate (ORR) in PD-L1 positive (PD-L1 ≥1%) and PD-L1 negative (PD-L1 \<1%) participants was defined as the percentage of treated participants with confirmed complete response (CR) or partial response (PR) per RECIST 1.1 based on Blinded Independent Central Review (BICR) assessment.
Number of Participants With Dose Limiting Toxicities (DLTs) - Part 2
时间窗: 9 weeks after first dose
Dose limiting toxicities (DLTs) were defined as any of the items listed below. 1. Any Grade 2 drug-related uveitis or eye pain that does not respond to topical therapy and does not improve to Grade 1 severity within the re-treatment period OR requires systemic treatment. 2. Any Grade 2 drug-related pneumonitis or interstitial lung disease that does not resolve to dose delay and systemic steroids in 14 days. 3. Any Grade 3 non-skin drug-related adverse event with the exception of laboratory abnormalities that cannot be alleviated or controlled by appropriate care within 14 days. 4. Any Grade 4 drug-related adverse event including laboratory abnormalities except Grade 4 leukopenia or neutropenia lasting \< 14 days and asymptomatic amylase/lipase elevation. 5. Drug-related hepatic function laboratory abnormalities.
Number of Participants With Laboratory Abnormalities in Thyroid Tests - Part 2
时间窗: From first dose to 30 days post last dose
Number of participants with specific thyroid laboratory abnormalities graded by Common Terminology Criteria for Adverse Events (CTCAE v4.0) to determine the safety and tolerability of Nivolumab and Ipilimumab combined with chemotherapy.
次要结局
- Progression Free Survival (PFS) - Part 2(From first dose to the first date of documented progression, or death due to any cause, whichever occurred first (Up to approximately 59 months))
- Objective Response Rate (ORR) - Part 1(From first dose up to approximately 72 months)
- Objective Response Rate (ORR) - Part 2(From first dose up to approximately 59 months)
- Overall Survival (OS) - Part 2(From the date of first treatment to the date of death due to any cause (Up to approximately 59 months))
- Progression Free Survival (PFS) - Part 1(From first dose to the first date of documented progression, or death due to any cause, whichever occurred first (Up to approximately 72 months))
- Overall Survival (OS) by PD-L1 Expression Levels - Part 1(From the date of first treatment to the date of death due to any cause (Up to approximately 72 months))
- Progression Free Survival (PFS) by Tumor Mutation Burden (TMB) Levels - Part 1(From first dose to the first date of documented progression, or death due to any cause, whichever occurred first (Up to approximately 72 months))
- Overall Survival (OS) - Part 1(From the date of first treatment to the date of death due to any cause (Up to approximately 72 months))
- Progression Free Survival (PFS) by PD-L1 Expression Levels - Part 1(From first dose to the first date of documented progression, or death due to any cause, whichever occurred first (Up to approximately 72 months))
- Overall Survival (OS) by Tumor Mutation Burden (TMB) Levels - Part 1(From the date of first treatment to the date of death due to any cause (Up to approximately 72 months))
- Objective Response Rate (ORR) by PD-L1 Expression Levels-Part 1(From first dose up to approximately 72 months)
- Objective Response Rate (ORR) by Tumor Mutation Burden (TMB) Levels - Part 1(From first dose up to approximately 72 months)