A Study Of Nivolumab In Combination With Trametinib With Or Without Ipilimumab In Participants With Previously Treated Metastatic Colorectal Cancers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 325
- 试验地点
- 47
- 主要终点
- Dose Limiting Toxicities in Part 1 and Part 1A
研究概览
简要总结
The purpose of this study is to investigate treatment with nivolumab in combination with trametinib with or without ipilimumab in participants with previously treated cancer of the colon or rectum that has spread.
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
- •Histologically or cytologically confirmed previously treated metastatic colorectal cancer with adenocarcinoma histology and in Stage IV per American Joint Committee on Cancer (version 4.0) at study entry
- •Microsatellite status should be performed per local standard of practice, immunohistochemistry (IHC) and/or PCR. If IHC results are equivocal, PCR is required for determining microsatellite stable (MSS) status
- •Must have measurable disease per RECIST 1.
- •Participants with lesions in a previously irradiated field as the sole site of measurable disease will be permitted to enroll provided the lesion(s) have demonstrated clear progression and can be measured accurately
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1 at screening and on cycle 1 day 1 (C1D1)
排除标准
- •BRAF V600 mutant colorectal cancer
- •Active brain metastases or leptomeningeal metastases
- •Active, known or suspected autoimmune disease
- •Participants with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study treatment administration
- •History of interstitial lung disease or pneumonitis
- •Prior treatment with immune checkpoint inhibitors and mitogen-activated protein kinase enzymes (MEK) inhibitors
- •History of allergy or hypersensitivity to study drug components
- •Other protocol defined inclusion/exclusion criteria apply
研究组 & 干预措施
Part 1 Cohort 1 3rd Line (3L): nivolumab + trametinib
干预措施: Nivolumab (Biological)
Part 1 Cohort 1 3rd Line (3L): nivolumab + trametinib
干预措施: Trametinib (Drug)
Part 1A Cohort 2 2nd Line (2L): nivolumab + ipilimumab + trametinib
干预措施: Nivolumab (Biological)
Part 1A Cohort 2 2nd Line (2L): nivolumab + ipilimumab + trametinib
干预措施: Trametinib (Drug)
Part 1A Cohort 2 2nd Line (2L): nivolumab + ipilimumab + trametinib
干预措施: Ipilimumab (Biological)
Part 1A Cohort 3 (2L): nivolumab + ipilimumab + trametinib
干预措施: Nivolumab (Biological)
Part 1A Cohort 3 (2L): nivolumab + ipilimumab + trametinib
干预措施: Trametinib (Drug)
Part 1A Cohort 3 (2L): nivolumab + ipilimumab + trametinib
干预措施: Ipilimumab (Biological)
Part 2 Cohort 4 (3L): nivolumab + ipilimumab + trametinib
干预措施: Nivolumab (Biological)
Part 2 Cohort 4 (3L): nivolumab + ipilimumab + trametinib
干预措施: Trametinib (Drug)
Part 2 Cohort 4 (3L): nivolumab + ipilimumab + trametinib
干预措施: Ipilimumab (Biological)
Part 2 Cohort 5 (3L): Regorafenib
干预措施: Regorafenib (Drug)
Part 1B Cohort 6 (2L): nivolumab + ipilimumab + trametinib
干预措施: Nivolumab (Biological)
Part 1B Cohort 6 (2L): nivolumab + ipilimumab + trametinib
干预措施: Trametinib (Drug)
Part 1B Cohort 6 (2L): nivolumab + ipilimumab + trametinib
干预措施: Ipilimumab (Biological)
结局指标
主要结局
Dose Limiting Toxicities in Part 1 and Part 1A
时间窗: 4 weeks for Doublet Reginmen and 8 weeks for triplet Regimen
Dose Limiting Toxicities are defined as adverse events have to be at least possibly related to study treatment, and not to disease progression, be clinically relevant and a clinically relevant shift from baseline.
Clinical Laboratory Abnormalities in Part 1 and Part 1A: Specific Thyroid Tests
时间窗: Assessed from first dose date to 100 days after last dose of study therapy. (Approximately: Part 1: ~ 6.5 Months Part 1A: ~ 5.5 Months)
Number of participants with clinical laboratory abnormalities in specific thyroid tests
Safety Related Events in Part 1 and Part 1 A
时间窗: Assessed from first dose date to 100 days after last dose of study therapy. (Approximately: Part 1: ~ 6.5 Months Part 1A: ~ 5.5 Months)
Safety-related events in clinical trials include Adverse Events (AEs), Serious Adverse Events (SAEs), and deaths. An AE is any new or worsening medical issue in a participant receiving the study drug, regardless of its relation to the drug. This includes abnormal lab results, symptoms, or diseases. An SAE is a more severe AE that results in death, is life-threatening, requires or prolongs hospitalization, causes significant disability, involves a birth defect, or is deemed medically important-potentially jeopardizing the participant or requiring intervention, even if not immediately life-threatening. These definitions help ensure consistent reporting and evaluation of safety during clinical studies.
Clinical Laboratory Abnormalities in Part 1 and Part 1A: Specific Liver Tests
时间窗: Assessed from first dose date to 100 days after last dose of study therapy. (Approximately: Part 1: ~ 6.5 Months Part 1A: ~ 5.5 Months)
Number of participants with clinical laboratory abnormalities in specific liver tests.
Overal Response Rate in Part 1B and Part 2
时间窗: Approximately up to 30 Months
ORR is defined as the proportion of all treated participants whose BOR is either confirmed complete response (CR) or confirmed partial response (PR).
次要结局
- Objective Response Rate in Part 1 and Part 1A(From the first dosing date and the date of the initial objectively documented tumor progression or subsequent therapy date (Approximately up to 21 Months))
- Disease Control Rate in Part 1 and Part 1A(From the first dosing date and the date of the initial objectively documented tumor progression or subsequent therapy date (Approximately up to 21 Months))
- Duration of Response in Part 1 and Part 1A(Approximately up to 20 Months)
- Time to Response in Part 1 and Part 1A(From the first dosing date to the date of first documented CR or PR per RECIST 1.1. (Approximately on average 10 months))
- Progression Free Survival in Part 1 and Part 1A(from the first dosing date to the date of first objectively documented disease progression or death, whichever occurs first (Approximately up to 21 months))
- Overall Survival in Part 1 and Part 1A(Approximately up to 69 Months)
- Safety Related Events in Part 1B and Part 2(Assessed from first dose date to 100 days after last dose of study therapy. (Approximately: 6.8 Months))
- Clinical Laboratory Abnormalities in Part 1B and Part 2: Specific Thyroid Tests(Assessed from first dose date to 100 days after last dose of study therapy. (Approximately: 6.8 Months))
- Clinical Laboratory Abnormalities in Part 1B and Part 2: Specific Liver Tests(Assessed from first dose date to 100 days after last dose of study therapy. (Approximately: 6.8 Months))