A Phase Ib, Open-label, Multicenter, Dose Escalation Study of the Safety, Tolerability, and Pharmacokinetics of HM95573 in Combination With Either Cobimetinib or Cetuximab in Patients With Locally Advanced or Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 148
- 试验地点
- 9
- 主要终点
- Percentage of patients with Adverse Events, Serious Adverse Events, and Adverse Events of Special Interest as assessed by CTCAE v4.03
研究概览
简要总结
This study evaluates the safety, tolerability and pharmacokinetics of HM95573 In combination with either cobimetinib or cetuximab in patients with locally advanced or metastatic solid tumors.
详细描述
This is a Phase Ib, open-label, multicenter dose-escalation study designed to assess the safety, tolerability, and pharmacokinetics of oral dosing of HM95573 in combination with either cobimetinib or cetuximab in patients with histologically/cytologically confirmed, locally advanced, or metastatic solid tumors with RAS- or RAF-mutation for which standard therapies either do not exist or have proven ineffective or intolerable. Treatment will continue until disease progression, unacceptable toxicity, any other discontinuation criterion is met.
There are two stages of this study: Stage 1 and 1b, standard 3+3 dose escalation, and Stage 2, an indication-specific dose expansion. Stage 1 is designed to establish the combination MTD for cobimetinib and HM95573. Stage 1 consists of concurrent administration of cobimetinib and HM95573. Stage 1b, is designed to select the combination dose of cetuximab and HM95573 for expansion stage.
In Stage 2 expansion cohort I and II, the RD of cobimetinib and HM95573 with different dosing schedules or regimens might be investigated (which may be≤ MTDs established during dose escalation) in indication-specific expansion cohorts. Stage 2 expansion cohort III will further characterize the safety and tolerability of cetuximab in combination with HM95573.
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
- 19 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Stage 1
Dose-escalation
干预措施: HM95573, cobimetinib (Drug)
Stage 1b
Dose-escalation
干预措施: HM95573, cetuximab (Drug)
Stage 2 (Cohort I and II)
Dose-expansion
干预措施: HM95573, cobimetinib (Drug)
Stage 2 (Cohort III)
Dose-expansion
干预措施: HM95573, cetuximab (Drug)
结局指标
主要结局
Percentage of patients with Adverse Events, Serious Adverse Events, and Adverse Events of Special Interest as assessed by CTCAE v4.03
时间窗: up to approximately 3 years
Number of patients with DLTs
时间窗: 28 days
MTDs of HM95573 and cobimetinib, or HM95573 and cetuximab
时间窗: End of Stage 1, an approximately 2 years
Recommended Phase II dose (RPIID) of HM95573 and cobimetinib, or HM95573 and cetuximab
时间窗: End of Stage 1, an approximately 2 years
次要结局
- FDG-PET and molecular biomarkers assessed in pre- and post-treatment tumor tissues(Screening, Cycle1 Day15)
- Time to maximum concentration (Tmax) of HM95573 and cobimetinib, or HM95573 and cetuximab(Cycle1 Day1, Cycle1 Day15, Cycle1 Day21, Cycle2 Day1, Cycle3 Day1, Study completion, an approximately 2 years)
- Maximum Serum Concentration (Cmax) of HM95573 and cobimetinib, or HM95573 and cetuximab(Cycle1 Day1, Cycle1 Day15, Cycle1 Day21, Cycle2 Day1, Cycle3 Day1, Study completion, an approximately 2 years)
- Area Under the Concentration-Time Curve (AUC) of HM95573 and cobimetinib, or HM95573 and cetuximab(Cycle1 Day1, Cycle1 Day15, Cycle1 Day21, Cycle2 Day1, Cycle3 Day1, Study completion, an approximately 2 years)
- Preliminary assessment of the antitumor activity of HM95573 and cobimetinib, or HM95573 and cetuximab measured by RECIST v1.1.(Screening, During Days 22-28 (Day 25 ± 3 days) in Cycle 2 and 4, and then every 8 weeks (±7 days), until disease progression, assessed approximately 3 years)