Clinical Trials /

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

NCT04762602

Description:

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.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of HMPL-306 in Advanced Solid Tumors With IDH Mutations
  • 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

Clinical Trial IDs

  • ORG STUDY ID: 2020-306-GLOB2
  • NCT ID: NCT04762602

Conditions

  • Isocitrate Dehydrogenase Gene Mutation

Interventions

DrugSynonymsArms
HMPL-306Part 1 Dose Escalation Cohorts

Purpose

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.

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
    

Trial Arms

NameTypeDescriptionInterventions
Part 1 Dose Escalation CohortsExperimentalPatients from each cohort will be administered HMPL-306 orally QD
  • HMPL-306
Part 2 Dose Expansion CohortsExperimentalPatients from each cohort will be administered HMPL-306 orally QD at the recommended phase 2 dose
  • HMPL-306

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Part 1: Number of Subjects with Dose Limiting Toxicities (DLTs)
Time Frame:Up to 28 days after first dose of study drug
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Objective Response Rate (ORR)
Time Frame:From first dose of study drug to the time of progressive disease, assessed up to 36 months
Safety Issue:
Description:ORR is defined as the proportion of subjects with confirmed best overall tumor response of Complete Response (CR) or Partial Response (PR).
Measure:Clinical Benefit Rate (CBR)
Time Frame:From first dose of study drug to the time of progressive disease, assessed up to 36 months
Safety Issue:
Description:CBR is the proportion of subjects with stable disease (SD), confirmed PR or confirmed CR (CR+PR+SD).
Measure: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
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description: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.
Measure:Maximum serum drug concentration
Time Frame:PK weeks at screening through safety follow-up, assessed up to 36 months
Safety Issue:
Description:Blood samples will be obtained from all patients for determination of the maximum serum concentration of HMPL-306
Measure:Time to maximum concentration
Time Frame:PK weeks at screening through safety follow-up, assessed up to 36 months
Safety Issue:
Description:Blood samples will be obtained from all patients for determination time to maximum concentration of HMPL-306
Measure:Area under the concentration-time curve (AUC)
Time Frame:PK weeks at screening through safety follow-up, assessed up to 36 months
Safety Issue:
Description:Blood samples will be obtained from all patients for determination of the AUC of HMPL-306

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Hutchison Medipharma Limited

Trial Keywords

  • Cholangiocarcinoma
  • Skeletal chondrosarcoma
  • Glioma
  • IDH Mutation

Last Updated

February 21, 2021