A Multicenter, Open-Label, Phase I Study Evaluating the Safety and Tolerability of HMPL-306 in Subjects With Advanced or Metastatic Solid Tumors With IDH Mutations
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Hutchmed
- 入组人数
- 42
- 试验地点
- 11
- 主要终点
- Part 1: Number of Subjects with Dose Limiting Toxicities (DLTs)
研究概览
简要总结
An open label single-arm clinical trial to evaluate the safety, tolerability, PK, PD, and preliminary efficacy of HMPL-306 in advanced or metastatic solid tumors with IDH mutation.
详细描述
HMPL-306 is a dual IDH1/2 inhibitor
This is a phase 1, open-label, multicenter study to evaluate the safety and tolerability of HMPL-306 administered orally in the treatment of subjects with advanced or metastatic solid tumors with IDH mutation. The study consists of 2 parts: Part 1 (dose escalation) and Part 2 (dose expansion). The dose escalation part will determine the MTD/RP2D. The dose expansion part will administer the MTD/RP2D to mIDH-positive solid tumor malignancies including, but not limited to, cholangiocarcinoma, skeletal chondrosarcoma, low-grade glioma, perioperative low-grade glioma
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
- •Subjects are eligible for enrollment into this study if they meet any of the following criteria (NOTE: This is not an exhaustive list):
- •Subjects aged ≥18 years.
- •ECOG performance status 0 or 1
- •Subjects must have a documented IDH mutation per immunohistochemistry (IHC), polymerase chain reaction (PCR), or next generation sequencing (NGS) testing of tumor tissue.
- •Subjects must have histologically or cytologically documented, advanced or metastatic solid malignancy of any type that has recurred or progressed on available standard treatment and for which no curative therapy exists.
排除标准
- •Subjects are not eligible for enrollment into this study if they meet any of the following criteria (NOTE: This is not an exhaustive list):
- •Subjects who received an investigational agent <14 days prior to their first day of study drug administration
- •Subjects who are pregnant or breastfeeding
- •Subjects with an active severe infection, some treated infections and with an expected or with an unexplained fever >38.3°C during screening visits or on their first day of study drug administration.
- •Subjects with some current or prior heart conditions
- •Subjects taking medications that are known to prolong the QT interval may not be eligible
- •Subjects with immediately life-threatening, severe complications of leukemia such as uncontrolled bleeding, pneumonia with hypoxia or shock, and/or disseminated intravascular coagulation
- •Some subjects with some current or prior gastrointestinal or liver diseases
- •Subjects with inadequate organ function as defined by the protocol
研究组 & 干预措施
Part 1 Dose Escalation Cohorts
Patients from each cohort will be administered HMPL-306 orally QD
干预措施: HMPL-306 (Drug)
Part 2 Dose Expansion Cohorts
Patients from each cohort will be administered HMPL-306 orally QD at the recommended phase 2 dose
干预措施: HMPL-306 (Drug)
结局指标
主要结局
Part 1: Number of Subjects with Dose Limiting Toxicities (DLTs)
时间窗: Up to 28 days after first dose of study drug
DLT is defined as an adverse event (AE) that meets protocol defined DLT criteria during cycle 1 and is at least possibly related to study drug.
Part 1 and Part 2: Frequency and severity of AEs
时间窗: From the first dose of the study drug to 37 days after the last dose of study drug
次要结局
- Clinical Benefit Rate (CBR)(From first dose of study drug to the time of progressive disease, assessed up to 36 months)
- Progression-free Survival (PFS)(From first dose of study drug to the time of progressive disease or death due to any causes, whichever comes first, assessed up to 36 months)
- Objective Response Rate (ORR)(From first dose of study drug to the time of progressive disease, assessed up to 36 months)
- Duration of response (DoR)(From first dose of study drug to the time of disease relapse or death, whichever comes first, assessed up to 36 months)
- Time to maximum concentration(PK weeks at screening through safety follow-up, assessed up to 36 months)
- Area under the concentration-time curve (AUC)(PK weeks at screening through safety follow-up, assessed up to 36 months)
- Maximum serum drug concentration(PK weeks at screening through safety follow-up, assessed up to 36 months)