A Phase 1b/2 Open-label, Nonrandomized Study of FGFR Inhibitor Futibatinib in Combination With MEK-inhibitor Binimetinib in Patients With Advanced KRAS Mutant Cancer
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 38
- 试验地点
- 3
- 主要终点
- Objective Response Rate (ORR) in Part 2
研究概览
简要总结
Phase 1b/2 study to evaluate the FGFRi futibatinib in combination with the MEKi binimetinib in patients with advanced KRASmt tumors.
详细描述
This is an open-label, nonrandomized, uncontrolled Phase 1b/2 study to determine the recommended phase 2 dose (RP2D) of futibatinib in combination with binimetinib and to explore the preliminary antitumor activity of futibatinib in combination with binimetinib in patients with advanced KRASmt tumors.
The study will consist of two parts:
- Part 1: Dose-Escalation part to determine the RP2D and dosing schedule of futibatinib in combination with binimetinib in patients with advanced cancer disease
- Part 2: Dose-Expansion part to evaluate the preliminary antitumor activity of futibatinib in combination with binimetinib at the RP2D in patients with advanced KRASmt NSCLC
Patients will receive study treatment until progressive disease or any other discontinuation or withdrawal criterion is met.
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
- •Histologically confirmed advanced cancer of any tumor type (Part 1) or NSCLC with a confirmed KRAS mutation as determined by local results (Part 2)
- •Appropriate candidate for experimental therapy
- •For patients in Part 2 only: Patient has radiographically measurable disease per RECIST 1.1 criteria.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 or
- •Adequate cardiac function (Left ventricular ejection fraction (LVEF) ≥50% )
- •Adequate organ function
- •Must have tumor tissue specimen available (optional for patients in Part 1)
排除标准
- •History or current evidence of calcium and phosphate hemostasis disorder or systemic mineral imbalance with ectopic calcification of soft tissues
- •Current evidence or history of clinically significant corneal or retinal disorder as confirmed by ophthalmologic examination.
- •Known untreated central nervous system (CNS) metastases or history of uncontrolled seizures.
- •Significant gastrointestinal disorder(s) that could interfere with absorption of futibatinib/binimetinib
- •Patients who have neuromuscular disorders that are associated with elevated creatinine kinase (CK)
研究组 & 干预措施
Futibitanib in combination with binimetinib
Dose escalation: Futibitanib in combination with binimetinib in patients with advanced cancer disease.
Dose expansion: Futibatinib in combination with binimetinib at the RP2D in patients with advanced KRASmt NSCLC
干预措施: Futibatinib and Binimetinib (Drug)
结局指标
主要结局
Objective Response Rate (ORR) in Part 2
时间窗: approximately 24 months
proportion of patients who have achieved a PR or complete response (CR) according to RECIST 1.1.
Recommended Phase 2 Dose (RP2D) in Part 1
时间窗: 12 months
Determine RP2D of futibatinib in combination with binimetinib based on Dose Limiting Toxicities
次要结局
- PK: Area under the plasma concentration-time curve (AUC) of futibatinib, binimetinib, and AR00426032(approximately 24 months)
- Duration of response (DOR)(approximately 24 months)
- Disease control rate (DCR) at 24 months(approximately 24 months)
- PK: Time to reach maximum plasma concentration (Tmax) of futibatinib, binimetinib, and AR00426032(approximately 24 months)
- Pharmacokinetics (PK): Maximum plasma concentration (Cmax) of futibatinib, binimetinib, and AR00426032(approximately 24 months)
- PK: Accumulation ratio of Cmax and AUC (R) of futibatinib, binimetinib, and AR00426032(approximately 24 months)
- Progression-free survival (PFS)(approximately 24 months)
- Number of patients with treatment-emergent adverse events as assessed by CTCAE v5.0(Approximately 24 months)
- PK: Terminal elimination half-life (T1/2) of futibatinib, binimetinib, and AR00426032(approximately 24 months)
- PK: Minimum plasma concentration before administration (Cmin) of futibatinib, binimetinib, and AR00426032(approximately 24 months)