A Phase I, Multicenter, Open-label Study to Evaluate the Safety, Pharmacokinetics, Preliminary Efficacy of KNT-0916 in Subjects With Unresectable or Metastatic Solid Tumors With FGFR2 Alterations
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 151
- 试验地点
- 1
- 主要终点
- Dose-limiting Toxicity (DLT)
研究概览
简要总结
This is a Phase1, open-label, dose escalation and expansion study designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary efficacy of KNT-0916 in patients with unresectable or metastatic solid tumors harboring FGFR2 alterations who have failed prior systemic therapy. This study is divided into 2 parts, dose escalation part(part A), dose expansion part(partB).
详细描述
This study is divided into 2 parts, part a isNdesigned to explore the maximum toxicity dose (MTD) of KNT-0916 with an accelerated titration plus traditional "3+3" design; part b is designed to explore the elementary anti-neoplastic activity of KNT-0916 with recommended dose in patients with confirmed FGFR2 alterations through central laboratory testing.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically confirmed unresectable or metastatic solid tumor
- •Documented FGFR2 gene fusion, mutation, or amplification per testing of blood and/or tumor
- •Patient must have measurable disease per RECIST v1.1
- •Patient has ECOG performance status of 0-1
- •Patient must have disease that is refractory to standard therapy, disease that has not adequately responded to standard therapy, disease for which standard or curative therapy does not exist, or the patient must be intolerant to or have declined standard therapy
- •An expected survival of ≥ 12 weeks.
- •Adequate organ function, as measured by laboratory values
排除标准
- •Prior treatment with any FGFR2 target therapy.
- •Central nervous system metastasis with associated symptom and signs.
- •Clinically significant, uncontrolled cardiovascular disease.
- •History of interstitial lung disease, or infectious pneumonitis need heavy antibiotics therapy
- •As judged by the investigator, unsuitable for attending the study.
研究组 & 干预措施
Part B - expansion
Oral dose of KNT-0916 as determined during Part A Dose Escalation.
干预措施: KNT-0916 (Drug)
Part A - dose escalation
Dose escalation of KNT-0916 in patients with advanced solid tumors.
干预措施: KNT-0916 (Drug)
结局指标
主要结局
Dose-limiting Toxicity (DLT)
时间窗: 4 weeks
Maximum tolerated dose (MTD) or Maximum administered dose (MAD)
时间窗: 12 months
Incidence, relatedness, seriousness and severity of adverse events (AEs) per the National Cancer Institute Common Terminology Criteria for AE (NCI CTCAE) Version 5.0.
时间窗: 33 months
Recommended phase 2 dose (RP2D)
时间窗: 33 months
次要结局
- Overall survival (OS) assessed as per RECIST 1.1(33 months)
- Objective response rate (ORR) assessed as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1(33 months)
- Duration of response (DoR) assessed as per RECIST 1.1(33 months)
- Pharmacokinetic parameters including maximum plasma drug concentration (Cmax)(33 months)
- Disease control rate (DCR) assessed as per RECIST 1.1(33 months)
- Progression-free survival (PFS) assessed as per RECIST 1.1(33 months)
- Pharmacokinetic parameters including area under the plasma concentration versus time curve (AUC)(33 months)
- Pharmacokinetic parameters including half-life (t1/2)(33 months)
- Pharmacokinetic parameters including time to maximum concentration (Tmax)(33 months)
- Pharmacokinetic parameters including Apparent clearance (CL/F)(33 months)