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

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ClinicalTrials.gov Identifier: NCT04762602
Recruitment Status : Not yet recruiting
First Posted : February 21, 2021
Last Update Posted : February 21, 2021
Sponsor:
Information provided by (Responsible Party):
Hutchison Medipharma Limited

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

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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
Estimated 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


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




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



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

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: John Kauh, MD (973) 567-3151 johnk@hmplglobal.com
Contact: Alisha Khullar, MS 973 287 3081 Alishak@hmplglobal.com

Locations
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United States, Georgia
Emory University
Atlanta, Georgia, United States, 30322
Contact: Nina Kimball    404-778-8670    ndobbs@emory.edu   
Principal Investigator: Olatunji Alese, MD         
United States, Texas
The University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Contact: Shannon Bailey    877-632-6789    slbailey@mdanderson.org   
Principal Investigator: Filip Janku, MD         
Sponsors and Collaborators
Hutchison Medipharma Limited
Investigators
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Study Director: John Kauh HMPL
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Responsible Party: Hutchison Medipharma Limited
ClinicalTrials.gov Identifier: NCT04762602    
Other Study ID Numbers: 2020-306-GLOB2
First Posted: February 21, 2021    Key Record Dates
Last Update Posted: February 21, 2021
Last Verified: December 2020

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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:
Cholangiocarcinoma
Skeletal chondrosarcoma
Glioma
IDH Mutation