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Isocitrate Dehydrogenase Gene MutationPhase 1NCT04762602

A Study of HMPL-306 in Advanced Solid Tumors With IDH Mutations

A Phase 1 study testing HMPL-306 in people with Isocitrate Dehydrogenase Gene Mutation, run by Hutchmed at 11 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

An open label single-arm clinical trial to evaluate the safety, tolerability, PK, PD, and preliminary efficacy of HMPL-306 in advanced or metastatic solid tumors with IDH mutation. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Isocitrate Dehydrogenase Gene Mutation
What is being tested?
HMPL-306
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
42 participants
Where
11 sitesin 2 countries
Study dates
28 Feb 2021to 27 Feb 2025
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Subjects are eligible for enrollment into this study if they meet any of the following criteria (NOTE: This is not an exhaustive list):
  • Subjects aged ≥18 years.
  • ECOG performance status 0 or 1
  • Subjects must have a documented IDH mutation per immunohistochemistry (IHC), polymerase chain reaction (PCR), or next generation sequencing (NGS) testing of tumor tissue.
  • Subjects must have histologically or cytologically documented, advanced or metastatic solid malignancy of any type that has recurred or progressed on available standard treatment and for which no curative therapy exists.

Who cannot join

  • 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
Show all 9Show fewer
  • 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

Trial locations and contacts

11 sites in 2 countries.

11 sites in 2 countries

United States8 sites

  • Emory University

    Atlanta, Georgia, 30322

  • Houston Methodist

    Houston, Texas, 77030

  • The University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

  • University of Iowa

    Iowa City, Iowa, 52242

  • University of Kentucky

    Lexington, Kentucky, 40536

  • Thomas Jefferson University

    Philadelphia, Pennsylvania, 19107

  • UPMC Hillman Cancer

    Pittsburgh, Pennsylvania, 15232

  • Sarcoma Oncology Research Center

    Santa Monica, California, 90403

Other trials in United States

Spain3 sites

  • Hospital de la Santa creu i Sant Pau

    Barcelona, 08025

  • Hospital Universitari Vall d'Hebron

    Barcelona, 08035

  • Hospital Universitario 12 de Octubre

    Madrid, 28041

Other trials in Spain

About this study

Official title: A Multicenter, Open-Label, Phase I Study Evaluating the Safety and Tolerability of HMPL-306 in Subjects With Locally Advanced or Metastatic Solid Tumors With IDH Mutations

An open label single-arm clinical trial to evaluate the safety, tolerability, PK, PD, and preliminary efficacy of HMPL-306 in advanced or metastatic solid tumors with IDH mutation.

Read the detailed description

HMPL-306 is a dual IDH1/2 inhibitor

This is a phase 1, open-label, multicenter study to evaluate the safety and tolerability of HMPL-306 administered orally in the treatment of subjects with advanced or metastatic solid tumors with IDH mutation. The study consists of 2 parts: Part 1 (dose escalation) and Part 2 (dose expansion). The dose escalation part will determine the MTD/RP2D. The dose expansion part will administer the MTD/RP2D to mIDH-positive solid tumor malignancies including, but not limited to, cholangiocarcinoma, skeletal chondrosarcoma, low-grade glioma, perioperative low-grade glioma

Being tested
HMPL-306
Keywords
Cholangiocarcinoma, Skeletal chondrosarcoma, Glioma, IDH Mutation
Medical subject headings
Cholangiocarcinoma, Glioma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • HMPL-306Drug

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

Study groups in NCT04762602
Study groupRoleWhat they receive
Part 1 Dose Escalation CohortsExperimentalPatients from each cohort will be administered HMPL-306 orally QD
Receives: Drug: HMPL-306
Part 2 Dose Expansion CohortsExperimentalPatients from each cohort will be administered HMPL-306 orally QD at the recommended phase 2 dose
Receives: Drug: HMPL-306

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Part 1: 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, pharmacokinetics (PK) and pharmacodynamics (PD). The modified toxicity probability interval-2 design was used to perform dose escalation and planned to determine MTD/RP2D.

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

  2. Part 1: Number of Patients With Dose-limiting Toxicities (DLTs)

    DLT:occurrence of any of following treatment-emergent adverse events (TEAEs) during DLT assessment window unless clearly unrelated to study drug/judged by investigator as not clinically significant:

    1. Non-hematologic:TEAEs Grade >=4, Grade 3 except those which recovered to Grade <=1 within 3 days after supportive therapy administered for nausea,vomiting,diarrhea,constipation,fatigue,electrolyte imbalance;Grade 3 hypothyroidism, adrenal gland or pituitary insufficiency, and inflammatory reactions at tumor site \& Grade 3 hypertension downgraded to Grade <=1 within 1 week with appropriate supportive therapy.
    2. Hematologic:Grade >=3 febrile neutropenia;Grade 4 neutropenia or thrombocytopenia;Grade 3 thrombocytopenia with clinically significant bleeding in addition to that requiring transfusion;Grade 4 anemia requiring a dose delay of >=14 days.
    3. Any life-threatening complication/abnormality not covered in National Cancer Institute Common Terminology Criteria for AEs version(v) 5.0.

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

  3. Parts 1 and 2: Number of Patients With Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events (TESAEs)

    AE:unfavorable,unintended sign,symptom or disease temporally associated with use of study drug or other protocol-imposed drug, whether or not considered drug related. SAE:AE that resulted in death, was life threatening, inpatient hospitalization/prolongation of existing hospitalization, persistent/significant incapacity or substantial disruption of ability to conduct normal life functions, congenital anomaly/birth defect, important medical event that jeopardized patient and required medical/surgical intervention to prevent above outcome or signs, symptoms or clinical sequelae of suspected overdose of either study drug or a concomitant medication. 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 beyond 30 days after last dose or after start of subsequent anti-tumor therapy and treatment-related SAEs.

    Measured: From the first dose of study drug (Day 1) up to 30 days after the last dose of study drug, approximately 43 months for Part 1

Secondary outcomes (9)

  1. Parts 1 and 2: Objective Response Rate (ORR)

    ORR by response evaluation criteria in solid tumors (RECIST) v1.1 was defined as the percentage of patients with confirmed best overall response (BOR) of complete response (CR) or partial response (PR) as determined by the investigator. CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. ORR by response assessment in neuro-oncology criteria (RANO) was defined as the percentage of patients with a BOR of CR or PR or minor response (MR) as determined by the investigator using RANO criteria mentioned in protocol for glioma patients.

    Measured: Tumor assessments performed every 8 weeks (+/-1 week) from Cycle 1 Day 1 for the first 24 weeks and every 12 weeks (+/-2 weeks) thereafter until end of treatment or end of efficacy follow-up period, approximately 47 months for Part 1

  2. Parts 1 and 2: Disease Control Rate (DCR)

    DCR by RECIST v1.1 was defined as percentage of patients with BOR of CR, PR, or stable disease (SD) lasting at least 7 weeks as determined by investigator.CR: disappearance of all target lesions.PR: at least a 30% decrease in sum of diameters of target lesions, taking as reference baseline sum of diameters.SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Pd, taking as reference the smallest sum on study. Pd: at least 20% increase in sum of diameters of target lesions, taking as reference smallest sum on study (nadir), including baseline. In addition to relative increase of 20%, sum must also demonstrate an absolute increase of at least 5 millimeters (mm). The appearance of 1 or more new lesions was also considered progression. DCR by RANO was defined as percentage of patients with BOR of CR, PR, MR, or SD lasting at least 7 weeks as determined by investigator using RANO criteria mentioned in protocol for glioma patients.

    Measured: Tumor assessments performed every 8 weeks (+/-1 week) from Cycle 1 Day 1 for the first 24 weeks and every 12 weeks (+/-2 weeks) thereafter until end of treatment or end of efficacy follow-up period, approximately 47 months for Part 1

  3. Parts 1 and 2: Duration of Response (DoR)

    DoR by RECIST v1.1 was defined as the time from the first occurrence of confirmed PR or confirmed CR until Pd or death, whichever came first. CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. Pd: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (nadir), including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression. DoR by RANO was defined as the time from the first occurrence of CR or PR or MR using RANO criteria mentioned in protocol for glioma patients, until disease progression or death, whichever comes first. Due to early study termination, Part 2 was never initiated.

    Measured: Tumor assessments performed every 8 weeks (+/-1 week) from Cycle 1 Day 1 for the first 24 weeks and every 12 weeks (+/-2 weeks) thereafter until end of treatment or end of efficacy follow-up period, approximately 47 months for Part 1

  4. Parts 1 and 2: Time to Response (TTR)

    TTR by RECIST v1.1 was defined as the time from start of study treatment until the date of first documented objective response, either confirmed CR or confirmed PR (whichever status was recorded first). CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. TTR by RANO was defined as the time from start of study treatment until the date of first documented objective response, either CR or PR or MR (whichever status was recorded first) using RANO criteria mentioned in protocol for glioma patients. Due to early study termination, Part 2 was never initiated.

    Measured: Tumor assessments performed every 8 weeks (+/-1 week) from Cycle 1 Day 1 for the first 24 weeks and every 12 weeks (+/-2 weeks) thereafter until end of treatment or end of efficacy follow-up period, approximately 47 months for Part 1

  5. Parts 1 and 2: Progression-free Survival (PFS)

    PFS was defined as the time from the date of first administration of study drug until the first radiographic documentation of objective progression as assessed by investigator using RECIST v1.1 or RANO criteria for glioma patients, or death from any cause. As per RECIST v1.1: Pd: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (nadir), including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of 1 or more new lesions was also considered progression. Criteria for RANO as mentioned in protocol.

    Measured: Tumor assessments performed every 8 weeks (+/-1 week) from Cycle 1 Day 1 for the first 24 weeks and every 12 weeks (+/-2 weeks) thereafter until end of treatment or end of efficacy follow-up period, approximately 47 months for Part 1

  6. Parts 1 and 2: Maximum Observed Plasma Concentration (Cmax) of HMPL-306

    Blood samples were collected at the specified timepoints to determine Cmax of HMPL-306.

    Measured: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8 and 24 hours post-dose on Day 1 of Cycles 1 and 2 for Part 1

  7. Parts 1 and 2: Time to Peak Plasma Concentration (Tmax) of HMPL-306

    Blood samples were collected at the specified timepoints to determine Tmax of HMPL-306.

    Measured: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8 and 24 hours post-dose on Day 1 of Cycles 1 and 2 for Part 1

  8. Parts 1 and 2: Area Under the Plasma Concentration-Time Curve From 0 to 24 Hours (AUC0-24) of HMPL-306

    Blood samples were collected at the specified timepoints to determine AUC0-24 of HMPL-306.

    Measured: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8 and 24 hours post-dose on Day 1 of Cycles 1 and 2 for Part 1

  9. Parts 1 and 2: Maximum Inhibition Rate of Plasma 2-Hydroxyglutaric Acid (2-HG)

    Blood samples were collected at the specified timepoints to determine plasma concentrations of 2-HG which was a PD marker. The maximum inhibition rate of 2-HG for patients in different dose groups is presented.

    Measured: From screening (Day -28) until end of treatment, approximately 42 months for Part 1

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Feb 2021
  2. Study start28 Feb 2021
  3. Primary completion27 Feb 2025
  4. Study completion27 Feb 2025

Why it stopped: The study was terminated based on strategic evaluation of the clinical development of HMPL-306 with no safety concerns

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
42 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04762602
Sponsor's protocol ID
2020-306-GLOB2
Status last verified
Mar 2026
First submitted
6 Feb 2021
Last updated
27 Mar 2026
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing HMPL-306 in people with Isocitrate Dehydrogenase Gene Mutation, run by Hutchmed at 11 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 27 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in United States, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Mar 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part 1: Recommended Phase 2 Dose (RP2D) of HMPL-306 (time frame: From the first dose of study drug (Day 1) up to Day 28 of Cycle 1). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04762602.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Mar 2026.

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