A Multicenter, Randomized Controlled Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of HMPL-306 in Patients With Gliomas Harboring IDH1 and/or IDH2 Mutations
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- Hutchmed
- 入组人数
- 52
- 试验地点
- 1
- 主要终点
- Number of Subjects with Dose Limiting Toxicities (DLTs)
研究概览
简要总结
This study is a multicenter, randomized controlled Phase I clinical study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of HMPL-306 in patients with gliomas harboring IDH1 and/or IDH2 mutations
详细描述
HMPL-306 is a dual IDH1/2 inhibitor. This is a multicenter, randomized controlled phase I clinical study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of HMPL-306 in patients with gliomas harboring IDH1 and/or IDH2 mutations.
The study consists of 2 parts: Part 1 (safety lead-in phase) and Part 2 (perioperative phase). Part 1 will determine safety and DLT. Part 2 will administer the HMPL-306 or no treatment to mIDH-positive gliomas.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- •Fully informed about the study and voluntarily sign the informed consent form (ICF).
- •Age ≥ 18 years.
- •Safety Lead-In Phase: Patients with gliomas of a documented IDH1 and/or IDH2 mutation. Perioperative Study Phase: Patients with gliomas of definitive or suspected IDH1 and/or IDH2 mutations scheduled for surgery.
- •All patients must have at least one measurable lesion.
- •Karnofsky Performance Status (KPS) score ≥ 80% .
- •In the investigator's judgment, a life expectancy of ≥ 12 weeks.
- •Sufficient bone marrow and organ function.
排除标准
- •Previous treatment with IDH inhibitors.
- •Unresolved toxicity from previous antitumor treatments not reverted to ≤ Grade 1 (except for alopecia, skin pigmentation changes, and ≤ Grade 2 peripheral neuropathy).
- •Patients assessed by researchers to have high-risk or unstable conditions.
- •Having other malignancies or a history of other malignancies within 5 years prior to screening.
- •History of clinically significant liver disease, including active infection with viral hepatitis, or other active hepatitis, alcoholic liver disease, cirrhosis, etc.
- •Patients with HIV infection.
- •Pregnancy (positive pregnancy test before dosing) or currently breastfeeding women.
- •Presence of diseases or conditions affecting drug absorption.
- •Any other conditions, in the investigator's judgment, unsuitable for the study drug, will result in exclusion.
研究组 & 干预措施
Safety run-in
This phase plans to enroll patients with gliomas of IDH1 and/or IDH2 mutations. The DLT will be evaluated during the first 28 days after the initial dosage.
干预措施: HMPL-306 (Drug)
Perioperative study phase
This phase plans to enroll patients with gliomas of definitive or suspected IDH1 and/or IDH2 mutations, who are scheduled for surgery. Patients who meet the inclusion criteria will be randomized to groups A, B, or C, to receive or not receive HMPL-306 treatment before surgery.
干预措施: HMPL-306 (Drug)
结局指标
主要结局
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.
RP2D
时间窗: From first dose of study drug to the time of progressive disease, assessed up to 24 months on average
Determine the Phase II recommended dose (RP2D) of HMPL-306 in patients with gliomas harboring IDH1 and/or IDH2 mutations based on a comprehensive assessment.
次要结局
- Maximum serum drug concentration(PK/PD weeks at screening through safety follow-up, assessed up to 24 months on average)
- Time to maximum concentration(PK/PD weeks at screening through safety follow-up, assessed up to 24 months on average)
- Area under the concentration-time curve (AUC)(PK/PD weeks at screening through safety follow-up, assessed up to 24 months on average)
- Concentration of 2-HG in brain tumor tissue(PK/PD weeks at screening through safety follow-up, assessed up to 24 months on average)