HMPL-306 treatment for gliomas with IDH1 or IDH2 mutations.

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

This study will test whether HMPL-306, a drug that blocks mutant IDH1 and IDH2, is safe and shows early benefit in adults with IDH‑mutant gliomas.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 52 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Hutchmed (Industry-sponsored)
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT07025018 on ClinicalTrials.gov

What this trial studies

HMPL-306 is a dual IDH1/2 inhibitor being tested in a multicenter, randomized, controlled Phase I protocol for adults with IDH1- or IDH2‑mutant gliomas. The study has two parts: Part 1 is a safety lead‑in to determine dose‑limiting toxicities and tolerability, and Part 2 is a perioperative randomized comparison of pre‑surgical HMPL‑306 versus no pre‑surgical treatment. Key outcomes include safety, tolerability, pharmacokinetics, pharmacodynamics in tumor tissue, and preliminary signals of antitumor activity. Eligible patients are adults with measurable IDH‑mutant gliomas, adequate organ function, and KPS ≥80 who can attend participating sites (one listed: Huashan Hospital, Fudan University, Shanghai).

Who should consider this trial

Good fit: Adults (≥18) with measurable gliomas harboring documented or suspected IDH1 and/or IDH2 mutations, KPS ≥80, adequate organ and marrow function, and life expectancy ≥12 weeks.

Not a fit: Patients without IDH1/2 mutations, those previously treated with IDH inhibitors, with uncontrolled comorbidities, or recent other malignancies may not benefit or be eligible.

Why it matters

Potential benefit: If successful, HMPL‑306 could offer a targeted treatment that slows tumor growth and improves outcomes for patients with IDH‑mutant gliomas.

How similar studies have performed: Other IDH inhibitors have shown tolerability and early signs of activity in IDH‑mutant tumors including gliomas, but clinical benefit in brain tumors remains preliminary.

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.

Where this trial is running

Shanghai, Shanghai Municipality

• Huashan Hospital affiliated to Fudan University — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Principal investigator: Jinsong Wu — Huashan Hospital
• Study coordinator: Tinghua Song

Conditions Gliomas Harboring IDH1 and/or IDH2 Mutations; gliomas; randomized controlled; Multicenter; IDH1 mutations; IDH2 mutations; safety run-in; MRI/MRS examination