Clinical trial NCT07025018: Phase I Study of HMPL-306 for the Treatment of Gliomas With IDH1 and/or IDH2 Mutations
Official title: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Gliomas Harboring IDH1 and/or IDH2 Mutations
Keywords: gliomas
randomized controlled
Multicenter
IDH1 mutations
IDH2 mutations
safety run-in
MRI/MRS examination
Phase I
clinical study
pharmacokinetics (PK)
pharmacodynamics (PD)
efficacy
HMPL-306
perioperative study
Lead sponsor: Hutchmed
Sponsor class: INDUSTRY
First posted: 2025-06-17
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Subjects with Dose Limiting Toxicities (DLTs)
timeFrame: Up to 28 days after first dose of study drug
measure: RP2D
timeFrame: From first dose of study drug to the time of progressive disease, assessed up to 24 months on average
Secondary outcomes:
measure: Maximum serum drug concentration
timeFrame: PK/PD weeks at screening through safety follow-up, assessed up to 24 months on average
measure: Time to maximum concentration
timeFrame: PK/PD weeks at screening through safety follow-up, assessed up to 24 months on average
measure: Area under the concentration-time curve (AUC)
timeFrame: PK/PD weeks at screening through safety follow-up, assessed up to 24 months on average
measure: Concentration of 2-HG in brain tumor tissue
timeFrame: PK/PD weeks at screening through safety follow-up, assessed up to 24 months on average
Other outcomes:
measure: Objective Response Rate (ORR)
timeFrame: From first dose of study drug to the time of progressive disease, assessed up to 24 months on average
measure: Duration of response (DoR)
timeFrame: From first dose of study drug to the time of disease relapse or death, whichever comes first, assessed up to 24 months on average
measure: Progression-free Survival (PFS)
timeFrame: From first dose of study drug to the time of progressive disease or death due to any causes, whichever comes first, assessed up to 24 months
Locations:
city: Shanghai
country: China
facility: Huashan Hospital affiliated to Fudan University
state: Shanghai
Study officials:
affiliation: Huashan Hospital
name: Jingsong Wu
role: PRINCIPAL_INVESTIGATOR
affiliation: Hutchmed
name: Bo Zhang
role: STUDY_DIRECTOR
References: