HMPL-306 in Participants With Postoperative Residual or Recurrent Grade 2 Glioma Harboring IDH1 or IDH2 Mutations

A Randomized, Double-Blind, Placebo-Controlled, Multicenter Phase III Study to Evaluate the Efficacy and Safety of HMPL-306 in Participants With Postoperative Residual or Recurrent Grade 2 Glioma Harboring IDH1 or IDH2 Mutations

This study is a randomized, double-blind, placebo-controlled, multicenter Phase III clinical trial evaluating the efficacy and safety of HMPL-306 in participants with postoperative residual or recurrent grade 2 gliomas carrying IDH1 or IDH2 mutations.

Study Overview

• Status: Not yet recruiting
• Conditions: Grade 2 Astrocytoma or Oligodendroglioma With an IDH1 or IDH2 Mutation
• Intervention / Treatment: Drug: HMPL-306 tablet; Drug: Placebo

Detailed Description

This study plans to enroll approximately 210 participants with postoperative residual or recurrent grade 2 astrocytoma or oligodendroglioma carrying IDH1 or IDH2 mutations who have previously received only surgical treatment.

Participants meeting all enrollment eligibility criteria will be randomized in a 1:1 ratio to receive HMPL-306 250 mg or placebo matched to HMPL-306 administered orally once daily (QD). Participants will continue to receive study drug treatment in 28-day cycles until BIRC-confirmed PD, death, occurrence of intolerable toxicity, et al, whichever occurs first.

Participants in the placebo group with BIRC-confirmed PD, after evaluation, may cross over to the HMPL-306 group to receive HMPL-306 treatment.

• Study Type: Interventional
• Enrollment (Estimated): 210
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Lu Chen; Phone Number: 021 -2067 3000 - 5014; Email: Luc@hutch-med.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Have fully understood this study and voluntarily signed the ICF, willing to complete the planned visits, treatments, procedures, and laboratory tests during the study period;
2. Age ≥18 years old;
3. Patients with grade 2 oligodendroglioma or grade 2 astrocytoma;
4. Have confirmed presence of IDH1 or IDH2 gene mutation, and obtained chromosome 1p/19q status;
5. Have undergone at least 1 glioma surgery and have not received any other anti-glioma treatments, including chemotherapy and radiotherapy;
6. Confirmed by BIRC, at least 1 measurable non-enhancing lesion meeting RANO 2.0 criteria using two-dimensional magnetic resonance imaging (MRI) measurement at screening;
7. KPS ≥80;
8. As judged by the investigator, life expectancy of ≥12 months;
9. Adequate bone marrow, hepatic, renal, and coagulation function

Exclusion Criteria:

1. Previously received any other anti-glioma treatment except for surgery, including chemotherapy, radiotherapy, targeted therapy, immunotherapy, or biological therapy, etc.;
2. Participants assessed by the investigator as having high-risk factors, including but not limited to tumor involvement of the brainstem, or uncontrolled epilepsy;
3. Participants with concurrent other malignant tumors or a history of other malignant tumors within 5 years prior to randomization (excluding cured basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, and ductal carcinoma in situ of the breast, etc.);
4. Women who are pregnant (positive pregnancy test before medication) or breastfeeding;
5. Known allergy to any component of HMPL-306;
6. Administration of uridine diphosphate glucuronosyltransferase (UGT) 1A1 inhibitors or UGT1A3 inhibitors less than 1 week or 5 half-lives (whichever is longer) prior to randomization; administration of strong inducers of CYP3A less than 2 weeks or 5 half-lives (whichever is longer) prior to randomization;
7. Presence of diseases or conditions that affect drug absorption;
8. Participants will be excluded if there is any other disease, mental abnormality, metabolic abnormality, physical examination abnormality, or laboratory parameter abnormality of significant clinical significance, etc., which, in the investigator's judgment, may affect the participant's compliance, or place the participant at high risk, or affect the interpretation of study results, or if there is reason to suspect that the participant has a disease or condition unsuitable for the use of the study drug.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HMPL-306 tablet; Participants in HMPL-306 group will receive HMPL-306 250 mg administered orally once daily (QD). Participants will continue to receive study drug treatment in 28-day cycles until BIRC-confirmed PD, death, occurrence of intolerable toxicity, et al, whichever occurs first.	Drug: HMPL-306 tablet; Participants meeting all enrollment eligibility criteria will be randomized in a 1:1 ratio to receive HMPL-306 or placebo matched to HMPL-306 administered orally once daily (QD). Participants in HMPL-306 group will receive HMPL-306 250 mg administered orally once daily (QD). Participants will continue to receive study drug treatment in 28-day cycles until BIRC-confirmed PD, death, occurrence of intolerable toxicity, et al, whichever occurs first.
Placebo Comparator: Placebo; Participants in placebo group will receive placebo matched to HMPL-306 administered orally once daily (QD). Participants will continue to receive study drug treatment in 28-day cycles until BIRC-confirmed PD, death, occurrence of intolerable toxicity, et al, whichever occurs first. Participants in the placebo group with BIRC-confirmed PD, after evaluation, may cross over to the HMPL-306 group to receive HMPL-306 treatment.	Drug: Placebo; Participants meeting all enrollment eligibility criteria will be randomized in a 1:1 ratio to receive HMPL-306 or placebo matched to HMPL-306 administered orally once daily (QD). Participants in placebo group will receive placebo matched to HMPL-306 administered orally once daily (QD). Participants will continue to receive study drug treatment in 28-day cycles until BIRC-confirmed PD, death, occurrence of intolerable toxicity, et al, whichever occurs first. Participants in the placebo group with BIRC-confirmed PD, after evaluation, may cross over to the HMPL-306 group to receive HMPL-306 treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS assessed by BIRC (according to Response Assessment in Neuro-Oncology [RANO] 2.0 criteria)	PFS(progression-free survival ):The time from the date of randomization to the date of first disease progression (PD) confirmed by BIRC(Blinded Independent Review Committee) or death from any cause	Up to approximately 30 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
TTNI	TTNI(time to next intervention ):The time from the date of randomization to the date of first initiation of any subsequent anti-tumor therapy or all-cause death	Up to approximately 36 months
TGR	TGR( tumor growth rate) :The time from the date of randomization to the date of first disease progression (PD) confirmed by BIRC or death from any cause	every 6months,up to approximately 30 months
TEAEs	Treatment-emergent adverse events (TEAEs) are defined as all adverse medical events that occur after participants receive the investigational medicinal product, which may manifest as symptoms, signs, diseases, or laboratory abnormalities, but are not necessarily causally related to the investigational medicinal product.	Up to approximately 30 months
PFS assessed by Investigator	PFS ( progression-free survival) : the time from the date of randomization to the date of first PD confirmed by investigators or all-cause death	Up to approximately 30 months
ORR	ORR(objective response rate),defined as the proportion of participants with best overall response of complete response (CR), partial response (PR), and minor response (MR)	Up to approximately 30 months
DCR	DCR(disease control rate), defined as the proportion of participants with best overall response of CR(complete response), PR(partial response), MR(minor response), and SD(Stable Disease )	Up to approximately 30 months
TTR	TTR(the time to response), defined as the time from the date of randomization to the date of first documented CR(complete response), PR(partial response), MR(minor response)	Up to approximately 30 months
DoR	DoR( duration of response), defined as the time from the date of first documented CR(complete response), PR(partial response), MR(minor response) to the date of first documented PD(Disease Progression) or death	Up to approximately 30 months
(CR+PR) Rate	CR+PR rate(the proportion of complete response and partial response), defined as the proportion of participants with best overall response of CR(complete response), and PR(partial response)	Up to approximately 30 months
Time to CR+PR	Time to CR+PR, defined as the time from the date of randomization to the date of first documented CR(complete response), or PR(partial response)	Up to approximately 30 months
Duration of CR+PR	Duration of CR+PR, defined as the time from the date of first documented CR or PR to the date of first documented PD or death from any cause, whichever occurs first	Up to approximately 30 months
OS	Overall survival (OS) :the time from the date of randomization to the date of all-cause death	Up to approximately 30 months
HRQoL (health-related quality of life)assessed by the FACT-Br (Functional Assessment of Cancer Therapy-Brain)questionnaire	The health-related quality of life (HRQoL) will be evaluated using the Functional Assessment of Cancer Therapy-Brain (FACT-Br) questionnaire in participants treated with HMPL-306 versus placebo	Up to approximately 30 months
PK characteristics(plasma drug concentrations at each sampling time point)	Plasma drug concentrations at each sampling time point	Up to approximately 6 months

Collaborators and Investigators

• Sponsor: Hutchmed
• Investigators: Principal Investigator: Jinsong Wu, MD, Huashan Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2026
• Primary Completion (Estimated): March 1, 2032
• Study Completion (Estimated): September 1, 2032

Study Registration Dates

• First Submitted: October 19, 2026
• First Submitted That Met QC Criteria: October 27, 2026
• First Posted (Actual): November 3, 2026

Study Record Updates

• Last Update Posted (Actual): November 3, 2026
• Last Update Submitted That Met QC Criteria: October 27, 2026
• Last Verified: October 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: 2026-306-00CH1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No