A Study of HMPL-306 in Advanced Hematological Malignancies With mIDH

NCT ID: NCT04764474

Last Updated: 2025-04-10

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 46 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-02-28
• Study Completion Date: 2025-01-15

Brief Summary

An open label single-arm clinical trial to evaluate the safety, tolerability, PK, PD, and preliminary efficacy of HMPL-306 in subjects with advanced relapsed, refractory, or resistant hematological malignancies that harbor IDH mutations.

Detailed Description

HMPL-306 is a dual IDH1/2 inhibitor

This is a phase 1, open-label, multicenter, single-arm study to evaluate safety, tolerability, PK, PD, and preliminary efficacy of HMPL-306 administered orally in treatment of subjects with advanced relapsed, refractory, or resistant hematological malignancies that harbor IDH mutations (or co-mutations).

The study consists of 2 parts: a dose-escalation part (Part 1) and a dose-expansion part (Part 2). The dose-escalation part will determine the MTD/R2PD. The dose-expansion part will administer the MTD/RP2D to subjects with mIDH-positive AML

Conditions

Isocitrate Dehydrogenase Gene Mutation

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment

All patients will be administered HMPL-306 orally QD

Group Type: EXPERIMENTAL

HMPL-306

Intervention Type: DRUG

Administered orally QD in a 28-day continuous dosing treatment cycle

Interventions

HMPL-306

Administered orally QD in a 28-day continuous dosing treatment cycle

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

Subjects may be enrolled in this study only if they satisfy all the following criteria (NOTE: This is not an exhaustive list):

• Subjects aged ≥18 years.
• ECOG performance status ≤ 2
• Subjects with advanced relapsed, refractory, or resistant hematological malignancies, as defined below:

Part 1:

• Subjects with documented IDH mutation per local or institutional next generation sequence (NGS).
• Subjects must be refractory to or intolerant of established therapies.
• Subjects who have received prior IDH inhibitor treatment may be enrolled in the escalation phase.

Part 2:

• Subjects with documented IDH mutation of any of these subsets: IDH1 (R132C), IDH1 (R132H), IDH (R140Q), and IDH2 (R172K), including co-mutations and any combination thereof per local and institutional NGS.
• Patients must have received at least 1 prior line of therapy with an IDH inhibitor. An established standard of care with proven benefit for which the patient is eligible, must not be available at the time of enrollment.
• Patients with AML must not have standard therapeutic options available (including IDH inhibitors where approved) and have the following:

• i. Relapsed AML unsuitable for intensive chemotherapy or venetoclax-based regimen or target agents;
• ii. Primary refractory AML unsuitable for intensive chemotherapy or venetoclax-based regimen or target agents.
• iii. Relapsed/refractory AML that has progressed on prior IDH treatment

Exclusion Criteria

Subjects are not eligible for enrollment into this study if they meet any of the following criteria (NOTE: This is not an exhaustive list):

• Subjects who received an investigational agent <14 days prior to their first day of study drug administration.
• Subjects who are pregnant or breastfeeding.
• Subjects with an active severe infection, some treated infections and with an expected or with an unexplained fever >38.3°C during screening visits or on their first day of study drug administration.
• Subjects with some current or prior heart conditions.
• Subjects taking medications that are known to prolong the QT interval may not be eligible.
• Subjects with immediately life-threatening, severe complications of leukemia such as uncontrolled bleeding, pneumonia with hypoxia or shock, and/or disseminated intravascular coagulation.
• Some subjects with some current or prior gastrointestinal or liver diseases.
• Subjects with inadequate organ function as defined by the protocol.
• Subjects with a medical condition, physical examination finding, or clinical laboratory finding that, in the Investigators opinion, contraindicates the use of an investigational drug or that may affect the interpretation of the results or renders the subject at high risk from treatment complications.
• Subjects with a known hypersensitivity to HMPL-306 or to any of its excipients.
• Subjects with presence of second primary malignant tumors within the last 2 years, with the exception of the following, if medically controlled: basal cell carcinoma of the skin, squamous cell carcinoma of the skin, carcinoma in situ of the cervix, and carcinoma in situ of the breast.
• Part 2 Only: The time since the last dose of prior IDH inhibitor treatment is within 30 days prior to the first day of study drug administration

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hutchmed

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bo Zhang

Role: STUDY_DIRECTOR

Hutchison Medipharma Limited

Locations

University of California Irvine Medical Center (UCIMC) - Chao Family Comprehensive Cancer Center

Orange, California, United States

Winship Cancer Institute - Emory University

Atlanta, Georgia, United States

University of Massachusetts Medical School

Worcester, Massachusetts, United States

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, United States

The Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Froedtert-Medical College of WI

Milwaukee, Wisconsin, United States

Clinica Universidad de Navarra

Pamplona, Navarre, Spain

Hospital Universitario Vall d'Hebron

Barcelona, , Spain

Institut Catala d'Oncologia de l'Hospitalet de Llobregat - Hospital Duran i Reynals

Barcelona, , Spain

START Madrid - Hospital Universitario Fundacion Jimenez Diaz

Madrid, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Hospital Universitario de Salamanca

Salamanca, , Spain

Hospital Clinico Universitario de Valencia

Valencia, , Spain

Hospital Universitario La Fe

Valencia, , Spain

Countries

United States; Spain

Other Identifiers

2020-306-GLOB1

Identifier Type: -

Identifier Source: org_study_id