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

NCT04764474 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: 2020-306-GLOB1
• Study Type: interventional
• Target: 46
• Locations: 2 countries
• Sites: 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.

Conditions

Isocitrate Dehydrogenase Gene Mutation

Keywords

Acute Myeloid Leukemia; IDH Mutation

Outcome Measures

Primary Outcomes (3)

• Dose Escalation Part: Recommended Phase 2 Dose (RP2D) of HMPL-306

  RP2D determination took the following criteria under consideration: determination of maximum tolerated dose (MTD) achieved during the dose escalation part and assessment of safety, PK and pharmacodynamics (PD).

  From the first dose of study drug (Day 1) up to Day 28 of Cycle 1

• Dose Escalation Part: Number of Patients With Dose-Limiting Toxicities (DLTs)

  DLT was defined as occurrence of any of the following treatment-emergent adverse events (TEAEs) during the DLT assessment window, unless clearly unrelated to the study drug as per investigator's discretion: nonhematologic toxicity: TEAEs of Grade \>=4, Grade \>=3 with the exception of those that resolved within 72 hours (h) of onset; hematologic toxicity with the exception of neutropenia or thrombocytopenia that occurred with active leukemic disease: Grade 3 or 4 neutropenia lasting more than 7 days, Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with bleeding or any requirement for platelets (PLT) transfusion, Grade 3 or greater febrile neutropenia defined as absolute neutrophil count (ANC) 1000 per cubic millimeter with a single temperature of \>38.3 degree Celsius (°C) or a sustained temperature of \>=38°C for more than 1 h; any TEAE requiring a dose delay of \>=14 days or cases of confirmed Hy's law.

  From the first dose of study drug (Day 1) up to Day 28 of Cycle 1

• Number of Patients With Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events (TESAEs)

  AE:unfavorable and unintended sign,symptom or disease temporally associated with use of study drug or other protocol-imposed intervention, whether or not considered related to study drug. SAE:AE that resulted in death,life-threatening AE,inpatient hospitalization/prolongation of existing hospitalization,persistent/significant incapacity or substantial disruption of ability to conduct normal life functions, abnormal pregnancy outcome in child born to female patient or female partner of male patient exposed to study drug or was important medical event that jeopardized patient and required medical/surgical intervention to prevent above outcome. TEAE:AE with onset on/after start of study drug until 30 days after last dose or prior to start of subsequent anti-tumor therapy, or AE with onset before start of study drug but worsened in severity after study drug administration, or AE onset after 30 days after last dose or after start of subsequent anti-tumor therapy and treatment-related SAEs.

  From the first dose of study drug (Day 1) up to 30 days after the last dose of study drug, approximately 25.25 months

Secondary Outcomes (14)

• Number of Patients With Best Overall Response (BOR)

  Tumor assessments performed every 8 weeks (+/-7 days) for the first 24 weeks and every 12 weeks (+/-14 days) thereafter until end of treatment, or end of efficacy follow-up period, approximately 45 months

• Objective Response Rate (ORR)

  Tumor assessments performed every 8 weeks (+/-7 days) for the first 24 weeks and every 12 weeks (+/-14 days) thereafter until end of treatment, or end of efficacy follow-up period, approximately 45 months

• Time to Objective Response (TTOR)

  Tumor assessments performed every 8 weeks (+/-7 days) for the first 24 weeks and every 12 weeks (+/-14 days) thereafter until end of treatment, or end of efficacy follow-up period, approximately 45 months

• Duration of Objective Response (DoOR)

  Tumor assessments performed every 8 weeks (+/-7 days) for the first 24 weeks and every 12 weeks (+/-14 days) thereafter until end of treatment, or end of efficacy follow-up period, approximately 45 months

• Clinical Benefit Rate (CBR)

  Tumor assessments performed every 8 weeks (+/-7 days) for the first 24 weeks and every 12 weeks (+/-14 days) thereafter until end of treatment, or end of efficacy follow-up period, approximately 45 months

Study Arms (1)

Treatment

EXPERIMENTAL

All patients will be administered HMPL-306 orally QD

Drug: HMPL-306

Interventions

HMPL-306 DRUG

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

Treatment

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hutchmed: lead

Study Sites (15)

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

Orange, California, 92868, United States

Location

Winship Cancer Institute - Emory University

Atlanta, Georgia, 30322, United States

Location

University of Massachusetts Medical School

Worcester, Massachusetts, 01655, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08901, United States

Location

The Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Froedtert-Medical College of WI

Milwaukee, Wisconsin, 53226, United States

Location

Clinica Universidad de Navarra

Pamplona, Navarre, 31008, Spain

Location

Hospital Clinico Universitario de Valencia

Valencia, Valencia, 46010, Spain

Location

Hospital Universitario La Fe

Valencia, Valencia, 46026, Spain

Location

Hospital Universitario Vall d'Hebron

Barcelona, 08035, Spain

Location

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

Barcelona, 08908, Spain

Location

START Madrid - Hospital Universitario Fundacion Jimenez Diaz

Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario de Salamanca

Salamanca, 58-182, Spain

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Limitations and Caveats

The study was terminated based on strategic evaluation of the clinical development of HMPL-306 with no safety concerns.

Results Point of Contact

• Title: Wade Clutson
• Organization: HUTCHMED Limited

HMPL306@hutch-med.com

973-306-4490

Study Officials

• Bo Zhang

  Hutchison Medipharma Limited

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: January 19, 2021
• First Posted: February 21, 2021
• Study Start: April 12, 2021
• Primary Completion: January 15, 2025
• Study Completion: January 15, 2025
• Last Updated: January 29, 2026
• Results First Posted: January 29, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

ES (8); US (7)