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

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.

Inclusion criteria

• 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.

Exclusion criteria

• 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.