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

NCT07025018 | Recruiting Phase 1

• 1 other identifier: 2025-306-00CH1
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

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

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

Outcome Measures

Primary Outcomes (2)

• Number of Subjects with Dose Limiting Toxicities (DLTs)

  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.

  Up to 28 days after first dose of study drug

• RP2D

  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.

  From first dose of study drug to the time of progressive disease, assessed up to 24 months on average

Secondary Outcomes (4)

• Maximum serum drug concentration

  PK/PD weeks at screening through safety follow-up, assessed up to 24 months on average

• Time to maximum concentration

  PK/PD weeks at screening through safety follow-up, assessed up to 24 months on average

• Area under the concentration-time curve (AUC)

  PK/PD weeks at screening through safety follow-up, assessed up to 24 months on average

• Concentration of 2-HG in brain tumor tissue

  PK/PD weeks at screening through safety follow-up, assessed up to 24 months on average

Other Outcomes (3)

• Objective Response Rate (ORR)

  From first dose of study drug to the time of progressive disease, assessed up to 24 months on average

• Duration of response (DoR)

  From first dose of study drug to the time of disease relapse or death, whichever comes first, assessed up to 24 months on average

• Progression-free Survival (PFS)

  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

Study Arms (2)

Safety run-in

EXPERIMENTAL

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.

Drug: HMPL-306

Perioperative study phase

EXPERIMENTAL

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.

Drug: HMPL-306

Interventions

HMPL-306 DRUG

IDH small molecule inhibitor

Perioperative study phase; Safety run-in

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hutchmed: lead

Study Sites (1)

Huashan Hospital affiliated to Fudan University

Shanghai, Shanghai Municipality, 200040, China

RECRUITING

MeSH Terms

Conditions

Glioma

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Jinsong Wu

  Huashan Hospital

  PRINCIPAL INVESTIGATOR

• Bo Zhang

  Hutchmed

  STUDY DIRECTOR

Central Study Contacts

Tinghua Song

CONTACT

+86 21 2067 1822; tinghuas@hutch-med.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 28, 2025
• First Posted: June 17, 2025
• Study Start: July 15, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: August 1, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)