A Phase Ib/II, Multicenter, Study of LEE011 in Combination With LGX818 in Adult Patients With BRAF Mutant Melanoma.
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 28
- 试验地点
- 6
- 主要终点
- Phase II - Objective Response Rate (ORR)
研究概览
简要总结
To evaluate the safety, tolerability and efficacy of LEE011 and LGX818 when administered orally to patients with BRAF mutant melanoma.
详细描述
In response to developments in the treatment of melanoma, the sponsor reviewed the data from the ongoing study and decided to halt further enrollment of patients in the Phase Ib part of the study. Consequently, the Phase II part of the study was not performed. Early termination of the study was not due to any safety concerns.
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
- •Age ≥18 years.
- •Diagnosis of locally advanced or metastatic melanoma along with written documentation of BRAF V600 mutation.
- •ECOG performance status of 0 -
- •Patients enrolled into Phase Ib must have evidence of evaluable and/or measurable disease as determined by RECIST v1.
- •Patients enrolled into Phase II (BRAFi naïve and resistant) must have evidence of measurable disease as determined by RECIST v1.
- •Archival tumor tissue must be obtained for patients enrolled in Phase Ib and Phase II arm 1a/b- BRAFi naïve patients. If an archival tumor tissue is not available, a fresh tumor sample is acceptable.
- •For patients enrolled in the phase II arm 2, patients must agree to undergo a fresh tumor biopsy unless one was collected prior to study entry but at the time of disease relapse from the most recent BRAFi treatment.
排除标准
- •Symptomatic brain metastases.
- •Symptomatic or untreated leptomeningeal disease.
- •Patients with inadequate laboratory values during screening.
- •In the phase II BRAFi naïve arms (1a/b), prior exposure to CDK4/6 inhibitor (e.g., PD 0332991)
- •Impaired cardiac function or clinically significant cardiac diseases.
- •Impairment of gastro-intestinal (GI) function or GI disease that may significantly alter the absorption of LEE011 or LGX
- •Patients with concurrent severe and/or uncontrolled concurrent medical conditions.
- •Previous or concurrent malignancy.
- •Major surgery < 2 weeks before starting study treatment
- •Known diagnosis of human immunodeficiency virus (HIV) or hepatitis C.
- •Other protocol-defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
Phase Ib
Phase Ib will randomize 18 patients with BRAF mutant melanoma, who are naïve or who have progressed on prior therapy to evaluate the safety and tolerability of the combination of LEE011 and LGX818.
干预措施: LEE011 (Drug)
Phase Ib
Phase Ib will randomize 18 patients with BRAF mutant melanoma, who are naïve or who have progressed on prior therapy to evaluate the safety and tolerability of the combination of LEE011 and LGX818.
干预措施: LGX818 (Drug)
Phase II arm 1a
Phase II arm 1a will randomize 60 patients that are naïve to prior BRAF inhibitor therapy to LGX818+LEE011 to evaluate the effect of adding LEE011 to a BRAFi in this population.
干预措施: LEE011 (Drug)
Phase II arm 1a
Phase II arm 1a will randomize 60 patients that are naïve to prior BRAF inhibitor therapy to LGX818+LEE011 to evaluate the effect of adding LEE011 to a BRAFi in this population.
干预措施: LGX818 (Drug)
Phase II arm 1b
Phase II arm 1b will randomize 30 patients to LGX818. Single agent anti-tumor activity of LGX818 is comparable to other BRAFi that are either approved or in clinical trials. This single agent anti-tumor activity will be compared to that of the combination (LEE011 + LGX818) in the BRAFi naïve patient population.
干预措施: LGX818 (Drug)
Phase II arm 2
Phase II arm 2 will evaluate a single arm LEE011+LGX818 in 40 patients resistant to prior BRAF inhibitor therapy. Single agent LGX818 has shown limited activity in patients with melanoma who have failed prior BRAF inhibitor treatment; the contribution of LEE011 in this combination will be evaluated.
干预措施: LEE011 (Drug)
Phase II arm 2
Phase II arm 2 will evaluate a single arm LEE011+LGX818 in 40 patients resistant to prior BRAF inhibitor therapy. Single agent LGX818 has shown limited activity in patients with melanoma who have failed prior BRAF inhibitor treatment; the contribution of LEE011 in this combination will be evaluated.
干预措施: LGX818 (Drug)
结局指标
主要结局
Phase II - Objective Response Rate (ORR)
时间窗: Approximately 23 months after enrollment
As per RECIST v1.1, ORR is defined as the proportion of patients with a best overall response of complete response or partial response. Due to the halt of enrollment during the Phase Ib part of the study, all analyses related to efficacy were not performed.
Phase Ib - Incidence of Dose Limiting Toxicities (DLTs) in Cycle 1
时间窗: Cycle 1 (approximately 28 days)
Dose Limiting Toxicities (DLTs) during the first 28 days of the combination treatment of LEE011 and LGX818. Due to the halt of enrollment, no Maximum Tolerated Dose (MTD) was formally declared during the study.
Phase II - Progression Free Survival (PFS)
时间窗: Approximately 23 months after enrollment
As per RECIST v1.1, PFS is the time from date of randomization/ start of treatment to the date of event defined as the first documented progression or death due to any cause. Due to the halt of enrollment during the Phase Ib part of the study, all analyses related to efficacy were not performed.
次要结局
- Phase II - Overall Survival (OS)(Approximately 23 months after enrollment)
- Phase Ib/II - Pharmacokinetic Parameters: Cmin(28-day cycles)
- Phase Ib/II - Plasma Concentration-time Profiles(28-day cycles)
- Phase Ib/II - Overall Response Rate (ORR)(Approximately 23 months after enrollment)
- Phase Ib/II - Progression Free Survival (PFS)(Approximately 23 months after enrollment)
- Phase Ib/II - Pharmacokinetic Parameters: Tmax(28-day cycles)
- Phase Ib/II - Pharmacokinetic Parameters: Racc(28-day cycles)
- Phase I - Number of Subjects Experiencing at Least One Adverse Event (AE).(Approximately 23 months after enrollment)
- Phase Ib/II - Pharmacokinetic Parameters: Cmax(28-day cycles)
- Phase I - Number of Subjects Experiencing at Least One Serious Adverse Event (SAE).(Approximately 23 months after enrollment)
- Phase Ib/II - Duration Of Response (DOR)(Approximately 23 months after enrollment)
- Phase Ib/II - Pharmacokinetic Parameters: AUCtau(28-day cycles)