A Study of HMPL-306 in Advanced Hematological Malignancies With mIDH
![]() |
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT04764474 |
Recruitment Status :
Recruiting
First Posted : February 21, 2021
Last Update Posted : March 9, 2022
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
Condition or disease | Intervention/treatment | Phase |
---|---|---|
Isocitrate Dehydrogenase Gene Mutation | Drug: HMPL-306 | Phase 1 |
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 hematological malignancies including, but not limited to, AML, MDS/MPN, AITL.
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 75 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | A Phase 1, Open-Label, Multicenter Study of HMPL-306 in Advanced Hematological Malignancies With Isocitrate Dehydrogenase (IDH) Mutations |
Actual Study Start Date : | February 28, 2021 |
Estimated Primary Completion Date : | January 31, 2023 |
Estimated Study Completion Date : | January 31, 2023 |

Arm | Intervention/treatment |
---|---|
Experimental: Treatment
All patients will be administered HMPL-306 orally QD
|
Drug: HMPL-306
Administered orally QD in a 28-day continuous dosing treatment cycle |
- Part 1: Number of Subjects with Dose Limiting Toxicities (DLTs) [ Time Frame: Up to 28 days after first dose of study drug ]DLT is defined as an adverse event (AE) that meets protocol defined DLT criteria during cycle 1 and is at least possibly related to study drug.
- Part 1 and Part 2: Frequency and severity of AEs [ Time Frame: From the first dose of the study drug to 37 days after the last dose of study drug ]
- Number of Subjects with Complete Response (CR) [ Time Frame: From 1st dose of study drug to the time of progressive disease, assessed up to 36 months ]
- Number of Subjects with Complete Response with Incomplete Marrow Recovery (CRi [ Time Frame: From 1st dose of study drug to the time of progressive disease, assessed up to 36 months ]
- Number of Subjects with Complete Response with Negative Minimal Residual Disease (CRMRD-) [ Time Frame: From 1st dose of study drug to the time of progressive disease, assessed up to 36 months ]
- Number of Subjects with Partial Response (PR) [ Time Frame: From 1st dose of study drug to the time of progressive disease, assessed up to 36 months ]
- Number of Subjects with Stable Disease (SD) [ Time Frame: From 1st dose of study drug to the time of progressive disease, assessed up to 36 months ]Subjects who have not achieved a CR, CRi, CRMRD-, morphologically leukemia-free state (MLFS), or PR but have no evidence of progression of disease in >8 weeks.
- Objective Response Rate (ORR) [ Time Frame: From 1st dose of study drug to the time of progressive disease, assessed up to 36 months ]ORR is defined as the proportion of subjects achieving PR and better response during the study [CR + CRi + marrow CR/MLFS + PR].
- Clinical Benefit Rate (CBR) [ Time Frame: From 1st dose of study drug to the time of progressive disease, assessed up to 36 months ]CBR is defined as the proportion of subjects achieving objective response or SD.
- Overall survival (OS) [ Time Frame: From first dose of study drug to end of study or death, assessed up to 36 months ]OS is defined as the time from the start of the study drug until death from any cause.
- Proportion of non-blood transfusion dependent subjects [ Time Frame: From the first dose of study drug to last dose of study drug, assessed up to 36 months ]It is defined as the proportion of subjects who do not need blood transfusion for any sequential period ≥8 weeks during the study treatment period.
- Maximum serum drug concentration [ Time Frame: PK weeks at screening through safety follow-up, assessed up to 36 months ]Blood samples will be obtained from all patients for determination of the maximum serum concentration of HMPL-306
- Time to maximum concentration [ Time Frame: PK weeks at screening through safety follow-up, assessed up to 36 months ]Blood samples will be obtained from all patients for determination time to maximum concentration of HMPL-306
- Area under the concentration-time curve (AUC) [ Time Frame: PK weeks at screening through safety follow-up, assessed up to 36 months ]Blood samples will be obtained from all patients for determination of the AUC of HMPL-306

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Key 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.
- Subjects must have received at least 2 prior lines of therapy for their hematologic malignancy.
- Subjects with MDS must have a Revised International Prognostic Scoring System (IPSS-R) score of >4.5 (high and very high risk).
- Subjects must not have progressed on prior IDH treatment unless isoform switching of the IDH mutation has been documented following progression on the prior IDH inhibitor.
Key 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.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04764474
Contact: Fiona Maxwell, MBBS, BSc, AKC, MRCP | 862-278-7789 | fionam@hutch-med.com | |
Contact: Martin Benes, PhD | +1-862-437-4309 | martinb@hutch-med.com |
United States, Georgia | |
Emory University | Recruiting |
Atlanta, Georgia, United States, 30322 | |
Contact: Shannon Gleason 404-727-6123 shannon.gleason@emory.edu | |
Principal Investigator: William Blum, MD | |
United States, New Jersey | |
Rutgers Cancer Institute of New Jersey | Recruiting |
New Brunswick, New Jersey, United States, 08901 | |
Contact: Dama Bhavsar 732-235-6008 bhavsadm@cing.rutgers.edu | |
Principal Investigator: Anupama Doraiswamy, MD | |
United States, Ohio | |
The Ohio State University Comprehensive Cancer Center | Recruiting |
Columbus, Ohio, United States, 43210 | |
Contact: Alice Mims, MD 614-685-6031 alice.mims@osumc.edu | |
Principal Investigator: Alice Mims, MD | |
United States, Texas | |
The University of Texas MD Anderson Cancer Center | Recruiting |
Houston, Texas, United States, 77030 | |
Contact: Rabiul Islam 281-908-8956 rislam@mdanderson.org | |
Principal Investigator: Farhad Ravandi-Kashani, MD | |
Spain | |
Hospital Universitario Vall d'Hebron | Recruiting |
Barcelona, Spain, 08035 | |
Contact: Antonieta Molero Yordi, MD 34932746000 amolero@vhio.net | |
Principal Investigator: Antoinieta Molero Yordi, MD | |
Institut Catala d'Oncologia de l'Hospitalet de Llobregat - Hospital Duran i Reynals | Recruiting |
Barcelona, Spain, 08908 | |
Contact: Arnan S Montserrat, MD 34932607750 marnan@iconcologia.net | |
Principal Investigator: Arnan S Montserrat, MD | |
Hospital Universitario 12 de Octubre | Recruiting |
Madrid, Spain, 28041 | |
Contact: Joaquin Martinez Lopez, MD,PhD 34932607750 jmarti01@med.ucm.es | |
Principal Investigator: Joaquin Martinez Lopez, MD, PhD |
Study Director: | Vijay Jayaprakash, MBBS, PHD | Hutchison Medipharma Limited |
Responsible Party: | Hutchison Medipharma Limited |
ClinicalTrials.gov Identifier: | NCT04764474 |
Other Study ID Numbers: |
2020-306-GLOB1 |
First Posted: | February 21, 2021 Key Record Dates |
Last Update Posted: | March 9, 2022 |
Last Verified: | February 2022 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Acute Myeloid Leukemia Myelodysplastic Syndrome Myeloproliferative Neoplasm Angio-Immunoblastic T-Cell Lymphoma IDH Mutation |
Hematologic Neoplasms Neoplasms Neoplasms by Site Hematologic Diseases |