Phase I Study of HMPL-306 for the Treatment of Gliomas With IDH1 and/or IDH2 Mutations

Официальное название

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

Обзор

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

Подробное описание

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.

Вмешательства

• Препарат HMPL-306
  IDH small molecule inhibitor

Первичные конечные точки

• Number of Subjects with Dose Limiting Toxicities (DLTs) [Срок оценки: Up to 28 days after first dose of study drug]
• RP2D [Срок оценки: From first dose of study drug to the time of progressive disease, assessed up to 24 months on average]

Вторичные конечные точки (4)

• Maximum serum drug concentration [Срок оценки: PK/PD weeks at screening through safety follow-up, assessed up to 24 months on average]
• Time to maximum concentration [Срок оценки: PK/PD weeks at screening through safety follow-up, assessed up to 24 months on average]
• Area under the concentration-time curve (AUC) [Срок оценки: PK/PD weeks at screening through safety follow-up, assessed up to 24 months on average]
• Concentration of 2-HG in brain tumor tissue [Срок оценки: PK/PD weeks at screening through safety follow-up, assessed up to 24 months on average]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Huashan Hospital affiliated to Fudan University — Шанхай

Идентификаторы

NCT: NCT07025018 · 2025-306-00CH1

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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