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

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ClinicalTrials.gov Identifier: NCT04764474
Recruitment Status : Recruiting
First Posted : February 21, 2021
Last Update Posted : March 9, 2022
Sponsor:
Information provided by (Responsible Party):
Hutchison Medipharma Limited

Study Description
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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.

Condition or disease Intervention/treatment Phase
Isocitrate Dehydrogenase Gene Mutation Drug: HMPL-306 Phase 1

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 hematological malignancies including, but not limited to, AML, MDS/MPN, AITL.

Study Design
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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

Resource links provided by the National Library of Medicine


Arms and Interventions
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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


Outcome Measures
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Primary Outcome Measures :
  1. 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.

  2. 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 ]

Secondary Outcome Measures :
  1. 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 ]
  2. 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 ]
  3. 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 ]
  4. 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 ]
  5. 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.

  6. 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].

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. 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

  12. 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


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
Contacts and Locations
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Information from the National Library of Medicine

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


Contacts
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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

Locations
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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         
Sponsors and Collaborators
Hutchison Medipharma Limited
Investigators
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Study Director: Vijay Jayaprakash, MBBS, PHD Hutchison Medipharma Limited
More Information
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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

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Hutchison Medipharma Limited:
Acute Myeloid Leukemia
Myelodysplastic Syndrome
Myeloproliferative Neoplasm
Angio-Immunoblastic T-Cell Lymphoma
IDH Mutation
Additional relevant MeSH terms:
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Hematologic Neoplasms
Neoplasms
Neoplasms by Site
Hematologic Diseases