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

Phase 1

Not yet recruiting

• Conditions: Gliomas Harboring IDH1 and/or IDH2 Mutations
• Interventions: Drug: HMPL-306

• Registration Number: NCT07025018
• Lead Sponsor: Hutchmed

Brief Summary

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

Detailed 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.

Study Timeline

• Study First Submitted: 2025-05-28
• Status Verified: 2025-06
• Study First Submitted QC: 2025-06-09
• Last Update Submitted: 2025-06-09
• Study First Posted: 2025-06-17
• Last Update Posted: 2025-06-17
• Study Start: 2025-07
• Primary Completion: 2026-12
• Study Completion: 2027-12

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 52

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Safety run-in	HMPL-306	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.
Perioperative study phase	HMPL-306	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.

Primary Outcome Measures

Name	Time	Method
Number of Subjects with Dose Limiting Toxicities (DLTs)	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	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.

Secondary Outcome Measures

Name	Time	Method
Concentration of 2-HG in brain tumor tissue	PK/PD weeks at screening through safety follow-up, assessed up to 24 months on average	Brain tumor tissue will be obtained from suitable patients for determination concentration of 2-HG.
Maximum serum drug concentration	PK/PD weeks at screening through safety follow-up, assessed up to 24 months on average	Blood samples will be obtained from all patients for determination of the maximum serum concentration of HMPL-306.
Time to maximum concentration	PK/PD weeks at screening through safety follow-up, assessed up to 24 months on average	Blood samples will be obtained from all patients for determination time to maximum concentration of HMPL-306.
Area under the concentration-time curve (AUC)	PK/PD weeks at screening through safety follow-up, assessed up to 24 months on average	Blood samples will be obtained from all patients for determination of the AUC of HMPL-306

Trial Locations

Locations (1)

Huashan Hospital affiliated to Fudan University; 🇨🇳 Shanghai, Shanghai, China