A Phase 1b/2a Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of AMG 232 Combined With Trametinib and Dabrafenib or Trametinib in Adult Subjects With Metastatic Cutaneous Melanoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 31
- 试验地点
- 1
- 主要终点
- Subject incidence of treatment-emergent adverse events, Results of safety laboratory tests, vital sign measurements, ECG measurements, PK parameters; Progression-free Survival Rate
研究概览
简要总结
Phase 1b/2a, open-label, sequential dose escalation and expansion study of AMG 232 in combination with trametinib and dabrafenib in subjects with metastatic melanoma followed by a direct comparison of AMG 232 combined with trametinib and dabrafenib versus trametinib combined with dabrafenib alone.
详细描述
The study will be conducted in 3 parts: Part 1 - Dose Escalation, Part 2 - Dose Expansion and Part 3, a randomized Phase 2a.
In both part 1 and 2, subjects will be enrolled open-label into 1 of 2 arms. For both Arm 1 and Arm 2, the part 1 dose escalation is aimed at determining an AMG 232 maximum tolerated dose (MTD) with a fixed dose of the combination drug(s) and evaluating safety, tolerability, pharmacokinetics and pharmacodynamics of each combination. Part 2 dose expansion will enroll subjects to receive therapy with a dose and schedule of AMG 232 selected from the corresponding part 1 dose escalation. In part 2 subjects will be enrolled to confirm safety and tolerability and to assess clinical activity prior to proceeding to Part 3, Phase 2a. In Phase 2a, Subjects will be randomized open-label in a 1:1 ratio to receive AMG 232 in combination with trametinib plus dabrafenib versus trametinib plus dabrafenib alone.
Only Part 1 of the study was enrolled and the study did not proceed into Phase 2.
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
- •Subjects must have histologically or cytologically confirmed metastatic cutaneous or mucosal melanoma, Able to swallow and retain orally administered medication, Adequate hematological, renal, hepatic, and coagulation laboratory assessments
排除标准
- •Clinically significant bleeding within 4 weeks of screening, Current use of warfarin, factor Xa inhibitors, and direct thrombin inhibitors, Infection requiring anti-infective treatments within 1 week of study enrollment, Anti-tumor therapy, Major surgery within 28 days
研究组 & 干预措施
AMG 232 with Trametinib and Dabrabenib
Arm 1 of Part 1 and 2 and Part 3
干预措施: AMG 232 (Drug)
AMG 232 with Trametinib and Dabrabenib
Arm 1 of Part 1 and 2 and Part 3
干预措施: Trametinib (Drug)
AMG 232 with Trametinib and Dabrabenib
Arm 1 of Part 1 and 2 and Part 3
干预措施: Dabrafenib (Drug)
AMG 232 with Trametinib
Arm 2 of Part 1 and 2
干预措施: AMG 232 (Drug)
AMG 232 with Trametinib
Arm 2 of Part 1 and 2
干预措施: Trametinib (Drug)
Trametinib and Dabrafenib
Part 3
干预措施: Trametinib (Drug)
Trametinib and Dabrafenib
Part 3
干预措施: Dabrafenib (Drug)
结局指标
主要结局
Subject incidence of treatment-emergent adverse events, Results of safety laboratory tests, vital sign measurements, ECG measurements, PK parameters; Progression-free Survival Rate
时间窗: 36 months
Incidence and grade of treatment-emergent adverse events, including dose-limiting toxicities; AMG 232, trametinib, dabrafenib, and metabolite PK parameters; progression-free Survival
次要结局
- Time to and duration of overall response and duration of stable disease measured by CT or MRI and assessed per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1, Progression-free and Overall Survival(36 months)