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

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: NCT04762602
Recruitment Status : Recruiting
First Posted : February 21, 2021
Last Update Posted : May 8, 2023
Sponsor:
Information provided by (Responsible Party):
Hutchmed

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 advanced or metastatic solid tumors with IDH mutation.

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 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

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multicenter, Open-Label, Phase I Study Evaluating the Safety and Tolerability of HMPL-306 in Subjects With Advanced or Metastatic Solid Tumors With IDH Mutations
Actual Study Start Date : February 28, 2021
Estimated Primary Completion Date : September 30, 2023
Estimated Study Completion Date : September 30, 2023

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Part 1 Dose Escalation Cohorts
Patients from each cohort will be administered HMPL-306 orally QD
 Drug: HMPL-306
Administered orally QD in a 28-day continuous dosing treatment cycle
Experimental: Part 2 Dose Expansion Cohorts
Patients from each cohort will be administered HMPL-306 orally QD at the recommended phase 2 dose
 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. Objective Response Rate (ORR) [ Time Frame: From first dose of study drug to the time of progressive disease, assessed up to 36 months ]
    ORR is defined as the proportion of subjects with confirmed best overall tumor response of Complete Response (CR) or Partial Response (PR).

  2. Clinical Benefit Rate (CBR) [ Time Frame: From first dose of study drug to the time of progressive disease, assessed up to 36 months ]
    CBR is the proportion of subjects with stable disease (SD), confirmed PR or confirmed CR (CR+PR+SD).

  3. Duration of response (DoR) [ Time Frame: From first dose of study drug to the time of disease relapse or death, whichever comes first, assessed up to 36 months ]
    DoR defined as the time from the date of the first CR or PR to the first date of progressive disease (PD) or death from any cause.

  4. Progression-free Survival (PFS) [ Time Frame: From first dose of study drug to the time of progressive disease or death due to any causes, whichever comes first, assessed up to 36 months ]
    PFS is defined as time from first dose date of study drug to date of progression or date of death from any cause, whichever occurred first.

  5. 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

  6. 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

  7. 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 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.

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
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): NCT04762602


Contacts
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Contact: Martin Benes, PhD +1973306 ext 4490 martinb@hmplglobal.com
Contact: Warren Moore, MD 9733064490 warrenm@hutch-med.com

Locations
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United States, California
Sarcoma Oncology Research Center Recruiting
Santa Monica, California, United States, 90403
Contact: Victoria Chua    310-552-9999    vchua@sarcomaoncology.com   
Contact: Sant Chawla, MD    310-552-9999    santchawla@sarcomaoncology.com   
Principal Investigator: Sant Chawla, MD         
United States, Georgia
Emory University Recruiting
Atlanta, Georgia, United States, 30322
Contact: Andrew Arnett    404-778-0869    andrew.richard.arnett@emory.edu   
Contact: Olatunji Alese, MD    404-778-1900    olatunji.alese@emory.edu   
Principal Investigator: Olatunji Alese, MD         
United States, Iowa
University of Iowa Recruiting
Iowa City, Iowa, United States, 52242
Contact: Alyssa Pratt    319-356-4568    alyssa-pratt@uiowa.edu   
Contact: Varun Monga, MD    319-356-1616    varun-monga@uiowa.edu   
Principal Investigator: Varun Monga, MD         
United States, Kentucky
University of Kentucky Recruiting
Lexington, Kentucky, United States, 40536
Contact: Heather Health    859-323-6720    heather.flynn@uky.edu   
Contact: John Villano, MD    859-323-0405    jl.villano@uky.edu   
Principal Investigator: John Villano, MD         
United States, Pennsylvania
Thomas Jefferson University Recruiting
Philadelphia, Pennsylvania, United States, 19107
Contact: Suzanne O'Hara    215-955-1838    suzanna.ohara@jefferson.edu   
Contact: Jessica Burrell    215-955-1171    jessica.burrell@jefferson.edu   
Principal Investigator: John Glass, MD         
UPMC Hillman Cancer Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Gwendolyn Illar    412-623-5950    illargm@upmc.edu   
Contact: Julie Urban    412-623-7396    urbanj2@upmc.edu   
Principal Investigator: Melissa Burgess, MD         
United States, Texas
Houston Methodist Recruiting
Houston, Texas, United States, 77030
Contact: Caroline Fitzgerald, MD    713-441-1240    cfitzgerald3@houstonmethodist.org   
Principal Investigator: Maen Abdelrahim, MD         
The University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Hira Tariq    713-792-6080    htariq@mdanderson.org   
Contact: Jordi Rodon-Ahnert, MD    713-792-5603    jrodon@mdanderson.ord   
Principal Investigator: Jordi Rodon-Ahnert, MD         
Spain
Hospital de la Santa creu i Sant Pau Recruiting
Barcelona, Spain, 08025
Contact: Heidy Gutierrez    34935537633    HGutierrez@santpau.cat   
Principal Investigator: Georgia Anguera, MD         
Hospital Universitari Vall d'Hebron Recruiting
Barcelona, Spain, 08035
Contact: Joel Puig Sadurni    34 93 274 60 00 ext 4920    jpuig@vhio.net   
Contact: Maria Vieito, MD    34 93 489 30 00 ext 3685    mvieito@vhio.net   
Principal Investigator: Maria Vieito, MD         
Hospital Universitario 12 de Octubre Recruiting
Madrid, Spain, 28041
Contact: Jonathan Lucas    34 91 390 8339    jsantamaria.imas12@12o.es   
Contact: Sepulveda Sanchez, MD    34 91 390 8307    jmsepulveda76@gmail.com   
Principal Investigator: Sepulveda Sanchez, MD         
Sponsors and Collaborators
Hutchmed
Investigators
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Study Director: Vijay Jayaprakash, MD HMPL
More Information
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Responsible Party: Hutchmed
ClinicalTrials.gov Identifier: NCT04762602    
Other Study ID Numbers: 2020-306-GLOB2
First Posted: February 21, 2021    Key Record Dates
Last Update Posted: May 8, 2023
Last Verified: May 2023

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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 Hutchmed:
Cholangiocarcinoma
Skeletal chondrosarcoma
Glioma
IDH Mutation