Isocitrate Dehydrogenase Gene MutationPhase 1NCT04764474
A Study of HMPL-306 in Advanced Hematological Malignancies With mIDH
A Phase 1 study testing HMPL-306 in people with Isocitrate Dehydrogenase Gene Mutation, run by Hutchmed at 15 sites in 2 countries.
Trial 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. 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
- 46 participants
- Where
- 15 sitesin 2 countries
- Study dates
- 12 Apr 2021to 15 Jan 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 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).
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- 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
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.
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- 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
Trial locations and contacts
15 sites in 2 countries.
15 sites in 2 countries
Spain8 sites
Hospital Universitario Vall d'Hebron
Barcelona, 08035
Institut Catala d'Oncologia de l'Hospitalet de Llobregat - Hospital Duran i Reynals
Barcelona, 08908
START Madrid - Hospital Universitario Fundacion Jimenez Diaz
Madrid, 28040
Hospital Universitario 12 de Octubre
Madrid, 28041
Clinica Universidad de Navarra
Pamplona, Navarre, 31008
Hospital Universitario de Salamanca
Salamanca, 58-182
Hospital Clinico Universitario de Valencia
Valencia, Valencia, 46010
Hospital Universitario La Fe
Valencia, Valencia, 46026
United States7 sites
Winship Cancer Institute - Emory University
Atlanta, Georgia, 30322
The Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Froedtert-Medical College of WI
Milwaukee, Wisconsin, 53226
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08901
University of California Irvine Medical Center (UCIMC) - Chao Family Comprehensive Cancer Center
Orange, California, 92868
University of Massachusetts Medical School
Worcester, Massachusetts, 01655
About this study
Official title: A Phase 1, Open-Label, Multicenter Study of HMPL-306 in Advanced Hematological Malignancies With Isocitrate Dehydrogenase (IDH) Mutations
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.
Read the 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
- Being tested
- HMPL-306
- Keywords
- Acute Myeloid Leukemia, IDH Mutation
- Medical subject headings
- Leukemia, Myeloid, Acute
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 group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | All patients will be administered HMPL-306 orally QD Receives: Drug: HMPL-306 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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.
Measured: 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.
Measured: 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)
BOR was defined as the best response during the anti-tumor evaluation period, which was determined using time point responses (TPRs) from date of the first dose of study drug from Cycle 1 in continuous cycle up until the last evaluable TPR prior to or on the date of PD/relapse according to the 2017 European LeukemiaNet criteria, or death; or withdrawal of consent or lost to follow-up; or receiving subsequent anti-cancer therapy, whichever was earlier. Number of patients with BOR [complete response (CR), CR with negative minimal residual disease (CRmrd-), CR with partial hematological recovery (CRh), CR with incomplete count (CRi), morphologic leukemia-free state (MLFS), partial response (PR), stable disease (SD), and PD] are reported.
Measured: 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)
ORR was defined as the percentage of patients with BOR being CRmrd-, CR, CRh, CRi, MLFS or PR. CR: myeloblast <5%, blast cells without Auer bodies, no blast cells in peripheral blood, no extramedullary lesion, ANC >=1.0x10^9/L, PLT >=100x10^9/L. CRmrd-: CR with negative RT-qPCR or CR with negative MFC. CRi: met all other criteria of CR but ANC <1.0x10^9/L or PLT <100x10^9/L. MLFS: myeloblast <5%, blast cells without Auer bodies, no extramedullary lesion, no hematological recovery requirements. PR: met all hematological criteria for CR, percentage of myeloblasts decreased from baseline by least 50% and reached 5% to 25%.
Measured: 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)
TTOR was defined as the time from the date of first study drug administration from Cycle 1 in continuous cycle to the date of first objective response (CRmrd-, CR, CRh, CRi, MLFS, or PR). CR: myeloblast <5%, blast cells without Auer bodies, no blast cells in peripheral blood, no extramedullary lesion, ANC >=1.0x10^9/L, PLT >=100x10^9/L. CRmrd-: CR with negative RT-qPCR or CR with negative MFC. CRi: met all other criteria of CR but ANC <1.0x10^9/L or PLT <100x10^9/L. MLFS: myeloblast <5%, blast cells without Auer bodies, no extramedullary lesion, no hematological recovery requirements. PR: met all hematological criteria for CR, percentage of myeloblasts decreased from baseline by least 50% and reached 5% to 25%.
Measured: 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)
DoOR was defined as the time from the first occurrence of objective response (CRmrd-, CR, CRh, CRi, MLFS, or PR) until PD, relapse, or death due to any cause, whichever came first. CR: myeloblast <5%, blast cells without Auer bodies, no blast cells in peripheral blood, no extramedullary lesion, ANC >=1.0x10^9/L, PLT >=100x10^9/L. CRmrd-: CR with negative RT-qPCR or CR with negative MFC. CRi: met all other criteria of CR but ANC <1.0x10^9/L or PLT <100x10^9/L. MLFS: myeloblast <5%, blast cells without Auer bodies, no extramedullary lesion, no hematological recovery requirements. PR: met all hematological criteria for CR, percentage of myeloblasts decreased from baseline by least 50% and reached 5% to 25%.
Measured: 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)
CBR was defined as the percentage of patients with BOR being CRmrd-, CR, CRh, CRi, MLFS, PR, or SD lasting for 3 cycles. CR: myeloblast <5%, blast cells without Auer bodies, no blast cells in peripheral blood, no extramedullary lesion, ANC >=1.0x10^9/L, PLT >=100x10^9/L. CRmrd-: CR with negative RT-qPCR or CR with negative MFC. CRi: met all other criteria of CR but ANC <1.0x10^9/L or PLT <100x10^9/L. MLFS: myeloblast <5%, blast cells without Auer bodies, no extramedullary lesion, no hematological recovery requirements. PR: met all hematological criteria for CR, percentage of myeloblasts decreased from baseline by least 50% and reached 5% to 25%. SD: Not met criteria for CR, CRi, CRmrd-, MLFS, PR, or PD.
Measured: 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
Progression-Free Survival (PFS)
PFS was defined as the time from the start of study drug from Cycle 1 in continuous cycle to PD, or relapse, or death due to any cause, whichever occurred first. PD was defined as increase in bone marrow blast percentage and/or absolute peripheral blood blast cells: a) myeloblasts percentage increased from baseline by >50% (if blast cells at baseline were <30%, net increased value needs to be >=15%) or myeloblasts percentage >70% continued for at least 3 months; ANC was not seen to be improved by at least 100%, reached (>0.5x10^9/L and/or PLT reached >50x10^9/L, without blood transfusion); b) the absolute peripheral blood blast cell count (WBCxblast cell ratio) increased by >50% and reached >25x10^9/L (without differentiation syndrome); or new extramedullary diseases.
Measured: 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
Overall Survival (OS)
OS was defined as the time from the start of study drug from Cycle 1 in continuous cycle until the date of death due to any cause.
Measured: From the first dose of study drug (Day 1) up to date of death due to any cause, approximately 45 months
Event-Free Survival (EFS)
EFS was defined as the time from date of first study drug administration from Cycle 1 in continuous cycle to treatment failure, relapse from CR (including CRmrd-, CR, CRh and CRi), or death due to any cause, whichever occurred first. CR: myeloblast <5%, blast cells without Auer bodies, no blast cells in peripheral blood, no extramedullary lesion, ANC >=1.0x10^9/L, PLT >=100x10^9/L. CRmrd-: CR with negative RT-qPCR or CR with negative MFC. CRi: met all other criteria of CR but ANC <1.0x10^9/L or PLT <100x10^9/L. Treatment failure was defined as failure to achieve CR (including CRmrd-, CR, CRh, CRi) by Week 24. Patients who did not achieve CR (including CRmrd-, CR, CRh, CRi) by Week 24 were considered to have had an event at Day 1 of first study drug administration from Cycle 1 (excluding single oral dose from PK week). For remaining CR responders (including CRmrd-, CR, CRh and CRi), event time was time of either disease relapse or death due to any cause, whichever occurred first.
Measured: 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
Number of Patients With Post-Baseline Transfusion Independence (TI)
Post-baseline TI was defined as the absence of red blood cell and platelet transfusions for a pre-specified time during treatment period which was defined from the first dose of study drug administration from Cycle 1 in continuous cycle to 30 days after the last dose date or prior to the start of a subsequent anti-tumor therapy (whichever came first). Number of patients with post-baseline TI for >=4 weeks and >=8 weeks is presented.
Measured: From the first dose of study drug (Day 1) up to 30 days after the last dose of study drug, approximately 25.25 months
Plasma Concentrations of HMPL-306
Blood samples were collected at the specified timepoints to determine plasma concentrations of HMPL-306.
Measured: PK Week: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 24, 48, 72, 96, 120, 144, 168 hours post-dose on Day 1 PK week; Cycle 2 Day 1: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 24 hours post-dose on Cycle 2 Day 1
Maximum Observed Plasma Concentration (Cmax) of HMPL-306
Blood samples were collected at the specified timepoints to determine Cmax of HMPL-306.
Measured: PK Week: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 24, 48, 72, 96, 120, 144, 168 hours post-dose on Day 1 PK week; Cycle 2 Day 1: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 24 hours post-dose on Cycle 2 Day 1
Time to Reach the Maximum Plasma Concentration (Tmax) of HMPL-306
Blood samples were collected at the specified timepoints to determine Tmax of HMPL-306.
Measured: PK Week: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 24, 48, 72, 96, 120, 144, 168 hours post-dose on Day 1 PK week; Cycle 2 Day 1: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 24 hours post-dose on Cycle 2 Day 1
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: PK Week: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 24 hours post-dose on Day 1 PK week; Cycle 2 Day 1: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 24 hours post-dose on Cycle 2 Day 1
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 for patients in different dose groups are presented.
Measured: From PK Week Day 2 until end of treatment, approximately 24.25 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2021
- Study start12 Apr 2021
- Primary completion15 Jan 2025
- Study completion15 Jan 2025
Why it stopped: The study was terminated based on strategic evaluation of the clinical development of HMPL-306 with no safety concerns
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Isocitrate Dehydrogenase Gene MutationStudies of the same condition, open and under way.
- More trials run by HutchmedThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 46 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hutchmed
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bo Zhang, Study director, Hutchison Medipharma Limited
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04764474
- Sponsor's protocol ID
- 2020-306-GLOB1
- Status last verified
- Jan 2026
- First submitted
- 19 Jan 2021
- Last updated
- 29 Jan 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Open-Label, Multicenter Study of HMPL-306 in Advanced Hematological Malignancies With Isocitrate Dehydrogenase (IDH) Mutations
- ClinicalTrials.gov ID
- NCT04764474
- Acronym / sponsor ID
- 2020-306-GLOB1
- Conditions
- Isocitrate Dehydrogenase Gene Mutation
- Keywords
- Acute Myeloid Leukemia, IDH Mutation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was terminated based on strategic evaluation of the clinical development of HMPL-306 with no safety concerns
- Enrolment
- 46 participants (actual)
- Lead sponsor
- HutchmedIndustry (pharma, biotech, devices)
- Study start
- 12 Apr 2021 (actual)
- Primary completion
- 15 Jan 2025 (actual)
- Study completion
- 15 Jan 2025 (actual)
- First posted
- 21 Feb 2021 (actual)
- Results
- Posted 29 Jan 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Drug: HMPL-306All patients will be administered HMPL-306 orally QD |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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:
- Subjects with documented IDH mutation per local or institutional next generation sequence (NGS).
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HMPL-306Administered orally QD in a 28-day continuous dosing treatment cycle | Drug | Treatment |
Primary outcome
Dose Escalation Part: 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
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).
Dose Escalation Part: Number of Patients With Dose-Limiting Toxicities (DLTs)
Time frame: From the first dose of study drug (Day 1) up to Day 28 of Cycle 1
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.
Number of Patients With Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events (TESAEs)
Time frame: From the first dose of study drug (Day 1) up to 30 days after the last dose of study drug, approximately 25.25 months
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.
14 secondary outcomes
Number of Patients With Best Overall Response (BOR)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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
Progression-Free Survival (PFS)
Time frame: 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
Overall Survival (OS)
Time frame: From the first dose of study drug (Day 1) up to date of death due to any cause, approximately 45 months
Event-Free Survival (EFS)
Time frame: 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
Number of Patients With Post-Baseline Transfusion Independence (TI)
Time frame: From the first dose of study drug (Day 1) up to 30 days after the last dose of study drug, approximately 25.25 months
Plasma Concentrations of HMPL-306
Time frame: PK Week: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 24, 48, 72, 96, 120, 144, 168 hours post-dose on Day 1 PK week; Cycle 2 Day 1: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 24 hours post-dose on Cycle 2 Day 1
Maximum Observed Plasma Concentration (Cmax) of HMPL-306
Time frame: PK Week: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 24, 48, 72, 96, 120, 144, 168 hours post-dose on Day 1 PK week; Cycle 2 Day 1: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 24 hours post-dose on Cycle 2 Day 1
Time to Reach the Maximum Plasma Concentration (Tmax) of HMPL-306
Time frame: PK Week: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 24, 48, 72, 96, 120, 144, 168 hours post-dose on Day 1 PK week; Cycle 2 Day 1: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 24 hours post-dose on Cycle 2 Day 1
Area Under the Plasma Concentration-Time Curve From 0 to 24 Hours (AUC0-24) of HMPL-306
Time frame: PK Week: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 24 hours post-dose on Day 1 PK week; Cycle 2 Day 1: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 24 hours post-dose on Cycle 2 Day 1
Maximum Inhibition Rate of Plasma 2-Hydroxyglutaric Acid (2-HG)
Time frame: From PK Week Day 2 until end of treatment, approximately 24.25 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jan 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bo Zhang study director
Hutchison Medipharma Limited
15 sites in 2 countries: see every site and its status.
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 15 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 15 inclusion and 13 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 29 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in Spain, United States. 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 29 Jan 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?
Dose Escalation Part: 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?
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 29 Jan 2026; AzTrials last refreshed its copy on 6 Nov 2026.