An Open-Label, Multi-Center Study to Investigate the Objective Response Rate, Safety, and Pharmacokinetics of GSK1120212, a MEK Inhibitor, in BRAF Mutation-positive Melanoma Subjects Previously Treated With or Without a BRAF Inhibitor
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 97
- 试验地点
- 1
- 主要终点
- Number of Participants With Best Confirmed Response
研究概览
简要总结
MEK113583 is a Phase II open-label, multi-site study to investigate the objective response rate, safety, and pharmacokinetics of GSK1120212 in subjects with BRAF mutation-positive melanoma who were previously treated with or without a BRAF inhibitor. GSK1120212 is a potent and highly selective inhibitor of MEK activation and kinase activity.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 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
- •Metastatic cutaneous melanoma that was previously treated with: (Cohort A) a BRAF inhibitor either with or without other prior therapy. (Cohort B) at least 1 prior chemotherapy or immunotherapy, without treatment with a BRAF inhibitor.
- •Documented positive BRAF mutation (V600E, V600K, or V600D).
- •Subjects must provide archived tumor tissue or undergo fresh tumor biopsy prior to enrollment.
- •The subject must have a radiographically measurable tumor.
- •The subject is able to carry out daily life activities without significant difficulty (ECOG performance status score of 0 or 1).
- •Able to swallow and retain oral medication.
- •Sexually active subjects must use acceptable methods of contraception during the course of the study.
- •Adequate organ system function and blood cell counts.
排除标准
- •The subject has had major surgery or received certain types of cancer therapy within 21 days before starting the study.
- •Previous treatment with a MEK inhibitor.
- •Current use of a prohibited medication listed in the protocol.
- •Uncontrolled glaucoma.
- •Brain metastasis, unless previously treated with surgery or stereotactic radiosurgery, and the disease has been stable for at least 2 months prior to enrollment.
- •Current severe or uncontrolled systemic disease.
- •History of clinically significant heart, lung, or eye/vision problems.
- •Significant unresolved side effects from previous anti-cancer therapy.
- •The subject is pregnant or breastfeeding.
研究组 & 干预措施
Cohort A
Subjects who have had previous treatment with a BRAF inhibitor.
干预措施: GSK1120212 (Drug)
Cohort B
Subjects who have had previous chemotherapy or immunotherapy without a BRAF inhibitor.
干预措施: GSK1120212 (Drug)
结局指标
主要结局
Number of Participants With Best Confirmed Response
时间窗: From Baseline (Day 1) until the time of the first documented evidence of a confirmed complete response or partial response (up to approximately 25 weeks)
Best confirmed response was assessed by the Investigator per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Best response was measured either as a complete response (CR), defined as the disappearance of all target lesions and pathological lymph nodes \<10 millimeters (mm), or a partial response (PR), defined as at least a 30% decrease in the sum of the diameters of target lesions. To be assigned a status of confirmed CR or PR, a confirmatory disease assessment was required no less than 28 days after the criteria for response were first met.
Number of Participants With Best Confirmed Response in the Indicated Subgroups of Participants Previously Treated With Standard Therapy But Not BRAF Inhibitors
时间窗: From Baseline (Day 1) until the time of the first documented evidence of a confirmed CR or PR (up to approximately 25 weeks)
The number of participants with best confirmed response was analyzed for the following subgroups of participants previously treated with standard therapy but not BRAF inhibitors: (1) participants with prior (before the start of this study) brain metastases (mets); (2) participants without prior brain mets; (3) participants with BRAF mutation V600E; (4) participants with BRAF mutation V600E and no prior brain mets; and (5) participants with BRAF mutation V600K. Objective response was assessed per RECIST version 1.1. Objective response was measured either as CR, defined as the disappearance of all target lesions and pathological lymph nodes \<10 mm, or PR, defined as at least a 30% decrease in the sum of the diameters of target lesions. To be assigned a status of confirmed CR or PR, a confirmatory disease assessment was required no less than 28 days after the criteria for response were first met. Brain metastasis is a cancer that has spread to the brain from another location of the body.
Number of Participants With Best Unconfirmed Response at the Time of the Interim Analysis (Week 8)
时间窗: Week 8
An interim analysis was performed using data collected approximately 12 and 13 weeks after the 30th participant was enrolled in the prior BRAF inhibitor and prior standard therapy groups, respectively. The best unconfirmed response by the investigator per RECIST version 1.1 was assessed. The study design permitted stopping the study for futility if \<3 best confirmed responses were observed in the first 30 participants of each treatment arm after completing the first post-dose assessment at Week 8. Best response was measured as either a CR, defined as the disappearance of all target lesions and pathological lymph nodes \<10 millimeters, or a PR, defined as at least a 30% decrease in the sum of the diameters of target lesions.
次要结局
- Mean Plasma Concentrations(Day 15, pre-dose, 0.5-2 hours (hrs) post-dose, 2-4 hrs post-dose, and 4-8 hrs post-dose; Week 4, pre-dose; Week 8, pre-dose; Week 12, pre-dose)
- Progression-free Survival (PFS)(Baseline (Day 1) until the time of disease progression or death due to any cause (up to approximately 57 weeks))
- PFS in the Indicated Subgroups of Participants Previously Treated With Standard Therapy But Not BRAF Inhibitors(Baseline (Day 1) until the time of disease progression or death due to any cause (up to approximately 57 weeks))
- Overall Survival(Baseline (Day 1) until death due to any cause (up to 134 weeks))
- Duration of Tumor Response(From the time of the first documented evidence of a confirmed CR or PR until disease progression or death due to any cause (up to approximately 40 weeks))
- Number of Participants With Any Adverse Event (AE)(From the date of the first dose of study medication until 28 days after the last dose (up to 477 days))
- Number of Participants Who Survived Until 6 Months, 12 Months and 24 Months From Baseline(Month 6, Month 12 and Month 24)
- Number of Participants With Tumor Progression(Baseline (Day 1) until tumor progression (up to approximately 57 weeks))