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

HUTCHMED

Status and phase: Enrolling; Phase 1

Conditions: Gliomas Harboring IDH1 and/or IDH2 Mutations

Treatments: Drug: HMPL-306

Study type: Interventional

Funder types: Industry

Identifiers

NCT07025018

2025-306-00CH1

Details and patient eligibility

About

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

Full description

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.

Enrollment: 52 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Fully informed about the study and voluntarily sign the informed consent form (ICF).
2. Age ≥ 18 years.
3. 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.
4. All patients must have at least one measurable lesion.
5. Karnofsky Performance Status (KPS) score ≥ 80% .
6. In the investigator's judgment, a life expectancy of ≥ 12 weeks.
7. Sufficient bone marrow and organ function.

Exclusion criteria

1. Previous treatment with IDH inhibitors.
2. Unresolved toxicity from previous antitumor treatments not reverted to ≤ Grade 1 (except for alopecia, skin pigmentation changes, and ≤ Grade 2 peripheral neuropathy).
3. Patients assessed by researchers to have high-risk or unstable conditions.
4. Having other malignancies or a history of other malignancies within 5 years prior to screening.
5. History of clinically significant liver disease, including active infection with viral hepatitis, or other active hepatitis, alcoholic liver disease, cirrhosis, etc.
6. Patients with HIV infection.
7. Pregnancy (positive pregnancy test before dosing) or currently breastfeeding women.
8. Presence of diseases or conditions affecting drug absorption.
9. Any other conditions, in the investigator's judgment, unsuitable for the study drug, will result in exclusion.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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52 participants in 2 patient groups

Safety run-in

Experimental group

Description:

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.

Treatment:

Drug: HMPL-306

Perioperative study phase

Experimental group

Description:

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.

Treatment:

Drug: HMPL-306