A Phase 1/1b, Open-label, Multicenter Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Anti-tumor Activity of KIN-3248 in Participants With Advanced Tumors Harboring FGFR2 and/or FGFR3 Gene Alterations
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 54
- 试验地点
- 21
- 主要终点
- Part A (dose escalation) - incidence of adverse events (AEs)
研究概览
简要总结
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of KIN-3248, an oral small molecule FGFR inhibitor, in adults with advanced tumors harboring FGFR2 and/or FGFR3 gene alterations.
详细描述
This is a two-part, open label, multi-center, dose escalation and dose expansion study in participants with advanced tumors harboring FGFR2 and/or FGFR3 gene alterations.
Part A (dose escalation) is aimed at evaluating the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of KIN-3248, and determining the maximum tolerated dose (MTD) of daily dosing of KIN-3248.
Part B (dose expansion) may open once either the MTD and/or a biologically active dose of KIN-3248 is identified. Part B is aimed at evaluating the safety and efficacy of KIN-3248 at the recommended dose and schedule in participants with cancers harboring FGFR2 and/or FGFR3 gene alterations, including intrahepatic cholangiocarcinoma (ICC), urothelial cancer (UC), and other solid tumors.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Provide written informed consent prior to initiation of any study-specific procedures
- •Advanced stage solid tumor
- •Known FGFR2 and/or FGFR3 gene alteration, as confirmed by previous genomic analysis of tumor tissue or ctDNA
- •Measurable or evaluable disease according to RECIST v1.1
- •ECOG performance status 0 or 1
- •Adequate organ function, as measured by laboratory values (criteria listed in protocol)
- •Able to swallow, retain, and absorb oral medications
排除标准
- •Known clinically-active or clinically-progressive brain metastases from non-brain tumors
- •History and/or current evidence of abnormal calcium-phosphorous homeostasis, ectopic mineralization or calcification, or corneal or retinal disorder/keratopathy
- •GI tract disease causing an inability to take oral medication, malabsorption syndrome, requirement for intravenous alimentation, or uncontrolled inflammatory GI disease
- •Active, uncontrolled bacterial, fungal, or viral infection
- •Women who are lactating or breastfeeding, or pregnant
研究组 & 干预措施
Part A - dose escalation
Dose escalation of KIN-3248 in patients with solid tumors
干预措施: KIN-3248 (Drug)
Part B - dose expansion
Dose expansion evaluating the recommended dose and schedule of KIN-3248 identified from Part A
干预措施: KIN-3248 (Drug)
结局指标
主要结局
Part A (dose escalation) - incidence of adverse events (AEs)
时间窗: Initiation of study drug through 28 days after last dose (up to approximately 18 months)
Part B (dose expansion) - disease control rate (DCR): the proportion of participants who achieve stable disease, PR, or CR
时间窗: Initiation of study drug until disease progression (up to approximately 36 months)
Part A (dose escalation) - incidence of dose limiting toxicities (DLTs)
时间窗: Initiation of study drug through 28 days
Part B (dose expansion) - objective response rate (ORR): the proportion of participants who have achieved partial response (PR) or complete response (CR) according to RECIST v1.1
时间窗: Initiation of study drug until disease progression (up to approximately 36 months)
Part B (dose expansion) - duration of response (DOR): the length of time between initial tumor response to documented tumor progression
时间窗: Initiation of study drug until disease progression (up to approximately 36 months)
Part B (dose expansion) - progression-free survival (PFS): the length of time until documented tumor progression
时间窗: Initiation of study drug until disease progression (up to approximately 36 months)
次要结局
- Part A (dose escalation) - PK - time to reach maximum plasma concentration (Tmax) of KIN-3248(Initiation of study drug through Cycle 5 (up to approximately 4 months))
- Part A (dose escalation) - PK - area under the plasma concentration-time curve (AUC) of KIN-3248(Initiation of study drug through Cycle 5 (up to approximately 4 months))
- Part A (dose escalation) - PK - maximum plasma concentration (Cmax) of KIN-3248(Initiation of study drug through Cycle 5 (up to approximately 4 months))