Phase I Clinical Study on the Safety, Tolerance, Pharmacokinetics and Efficacy of YL-15293 in Patients With Advanced Solid Tumor With KRAS Mutation
试验速览
- 阶段
- 1 期
- 状态
- Enrolling By Invitation
- 入组人数
- 150
- 试验地点
- 1
- 主要终点
- Overall survival, OS
研究概览
简要总结
This is a phase 1 / 2 open label multicenter study to evaluate the maximum tolerance, safety, tolerance and PK of oral YL-15293 in patients with advanced solid tumors with KRAS mutation, so as to confirm the recommended phase 2 dose of YL-15293 and obtain the preliminary efficacy information of patients with advanced solid tumors with KRAS mutation.
详细描述
Dose escalation stage:
It is planned to include 21-42 subjects into 7 dose groups: 100mg/d, 200mg/d, 400mg/d, 600mg/d, 800mg/d, 1000mg/d and 1200mg/d. Three to six patients were enrolled in each dose group. 100mg/d is used as the initial dose. The dose of single administration phase is 100mg, qd, and the dose of multiple administration phase is 50mg, bid. The daily dose of the 1000mg/d dose group and above in the single administration stage is 1/2 of the daily dose, and the daily dose in the multiple administration stage is divided into two oral doses. The medication frequency (once or twice a day) and PK blood sampling point of the follow-up dose group are adjusted according to the PK parameters of the initial dose group. DLT evaluation is conducted in the first cycle (21 days).
Single-dose PK study: The drug was given once on an empty stomach in the morning on the first day, and the dose was half of the total dose of the day. Before administration (within 30 minutes before administration), pharmacokinetic samples were collected at 0.5, 1, 2, 3, 4, 6, 8, 10, and 24 hours after administration. A total of 10 blood sampling points were collected, with 4ml blood taken each time .
Multi-dose PK study: 7 days after a single dose, 21 days of continuous administration is a treatment cycle, 2 times a day. On the first day, the 7th day and the 21st day, within 30 minutes before the administration, and 0.5, 1, 2, 3, 4, 6, 8, 10, 24h after the administration on the 21st day, collect the pharmacokinetics Samples, a total of 12 blood collection points, 4ml blood each time.
In addition, in the presence of DLT and SAE, a blood sample must be collected immediately for pharmacokinetic analysis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
YL-15293
Single arm, open, single and multiple doses; Dosage form: YL-15293 tablets Specification: 50mg, 200mg Storage conditions: refrigerated and sealed at 2-8℃
Way of administration:
Single-dose study: Oral administration, once a day, with warm water, fasting administration, fasting 1 hour before and 2 hours after administration. Multiple administration studies: oral administration, warm water delivery, fasting administration, fasting 1 hour before administration and 2 hours after administration, continuous administration for 21 days as a treatment cycle. The way of taking the medicine is twice a day.
干预措施: YL-15293 (Drug)
结局指标
主要结局
Overall survival, OS
时间窗: Throughout the study for approximately 2 years
The time from randomization to death for any reason
The overall response rate (ORR)
时间窗: Throughout the study for approximately 2 years
The overall response rate (ORR) will be estimated based on the proportion of evaluable patients whose overall response (ORR) during study treatment is CR or PR. Disease response will be assessed by the investigator using RECIST v1.1.
Progression free survival, PFS
时间窗: Throughout the study for approximately 2 years
PFS, defined as the time from the first dose of study treatment to first
Disease control rate, DCR
时间窗: Throughout the study for approximately 2 years
The percentage of cases with remission (PR+CR) and stable lesions (SD) after treatment
次要结局
未报告次要终点