A First-in-human Phase 1 Dose-escalation Study Evaluating the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of KST-6051 in Patients With Advanced or Metastatic Solid Tumors With a KRAS Mutation
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 145
- 试验地点
- 9
- 主要终点
- Number of Participants With Treatment-emergent Adverse Events (TEAEs)
研究概览
简要总结
The main purpose of the trial is to assess whether the trial drug, KST-6051, is safe and tolerable when administered orally to adults with advanced or metastatic solid tumors with certain KRAS mutations.
详细描述
This is a first-in-human, phase 1, open-label, multicenter clinical trial designed to evaluate safety, tolerability, pharmacokinetics, biomarkers, pharmacodynamics and preliminary activity of orally administered KST-6051. The trial seeks to enroll adults with advanced or metastatic KRAS mutant solid tumors including but not limited to pancreatic ductal adenocarcinoma, colorectal cancer, and non-small cell lung cancer whose cancers have progressed after prior therapy or in whom standard therapy was not tolerated. The trial includes a dose escalation phase in which higher doses of KST-6051 will be given in subsequent groups of participants. Participants can stay in the trial as long as they benefit from the treatment and can tolerate it.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- •Age ≥ 18 years.
- •Willing and able to give written informed consent.
- •Histologically documented locally advanced and unresectable or metastatic NSCLC, PDAC, CRC, or other solid tumor.
- •Documentation of KRAS mutation prior to the first dose of trial drug(s).
- •Progressed on or intolerant to standard treatment(s).
- •Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or
- •Adequate cardiovascular, hematological, liver, and renal function.
- •Measurable disease at baseline per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1).
排除标准
- •Previous or current treatment with RAS or KRAS inhibitors.
- •Central nervous system (CNS) tumors or metastases.
- •Inability to swallow oral medications.
- •Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the trial.
- •Other inclusion/exclusion criteria are specified in the protocol.
研究组 & 干预措施
KST-6051 Dose Escalation
Sequential cohorts with increasing doses of KST-6051 will be evaluated to determine recommended dose(s) for expansion (RDE[s]).
干预措施: KST-6051 (Drug)
结局指标
主要结局
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
时间窗: Up to approximately 2 years
Clinically significant changes in safety assessments (vital signs, physical examinations, electrocardiograms, and clinical laboratory tests) are to be reported as adverse events.
Number of Participants With Treatment-related Adverse Events (TRAEs)
时间窗: Up to approximately 2 years
Clinically significant changes in safety assessments (vital signs, physical examinations, electrocardiograms, and clinical laboratory tests) are to be reported as adverse events.
Number of Participants With Dose-limiting Toxicities (DLTs) at the end of Cycle 1 (Each Cycle is 21 Days)
时间窗: Up to Day 21 of Treatment Cycle 1
次要结局
- Maximum Observed Blood Concentration (Cmax) of KST-6051(Up to Week 6)
- Time to Achieve Cmax (Tmax) of KST-6051(Up to Week 6)
- Half-life (t1/2) of KST-6051(Up to Week 6)
- Area Under the Blood Concentration-time Curve (AUC) of KST-6051(Up to Week 6)
- Objective Response Rate (ORR)(Up to approximately 2 years)
- Disease Control Rate (DCR)(Up to approximately 2 years)
- Duration of Overall Response (DOR)(Up to approximately 2 years)
- Progression-free Survival (PFS)(Up to approximately 2 years)
- Duration of Stable Disease(Up to approximately 2 years)