Phase I Study of HMPL-306 for the Treatment of Gliomas With IDH1 and/or IDH2 Mutations
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorHutchmed
About this trial
This study is a multicenter, randomized controlled Phase I clinical study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of HMPL-306 in patients with gliomas harboring IDH1 and/or IDH2 mutations
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Fully informed about the study and voluntarily sign the informed consent form (ICF).
Age ≥ 18 years.
Safety Lead-In Phase: Patients with gliomas of a documented IDH1 and/or IDH2 mutation. Perioperative Study Phase: Patients with gliomas of definitive or suspected IDH1 and/or IDH2 mutations scheduled for surgery.
All patients must have at least one measurable lesion.
Disqualifiers
Previous treatment with IDH inhibitors.
Unresolved toxicity from previous antitumor treatments not reverted to ≤ Grade 1 (except for alopecia, skin pigmentation changes, and ≤ Grade 2 peripheral neuropathy).
Patients assessed by researchers to have high-risk or unstable conditions.
Having other malignancies or a history of other malignancies within 5 years prior to screening.
Trial design
Design model
Sequential
Treatments tested in this trial
HMPL-306
DrugIDH small molecule inhibitor
Treatment groups
52 Participants
are divided into 2 treatment groupsGroup A: Safety run-inExperimental treatment 1 intervention
Group B: Perioperative study phaseExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Number of Subjects with Dose Limiting Toxicities (DLTs)
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.
Time frame
Up to 28 days after first dose of study drug2
RP2D
Determine the Phase II recommended dose (RP2D) of HMPL-306 in patients with gliomas harboring IDH1 and/or IDH2 mutations based on a comprehensive assessment.
Time frame
From first dose of study drug to the time of progressive disease, assessed up to 24 months on averageSecondary outcomes
1
Maximum serum drug concentration
Blood samples will be obtained from all patients for determination of the maximum serum concentration of HMPL-306.
Time frame
PK/PD weeks at screening through safety follow-up, assessed up to 24 months on average2
Time to maximum concentration
Blood samples will be obtained from all patients for determination time to maximum concentration of HMPL-306.
Time frame
PK/PD weeks at screening through safety follow-up, assessed up to 24 months on average3
Area under the concentration-time curve (AUC)
Blood samples will be obtained from all patients for determination of the AUC of HMPL-306
Time frame
PK/PD weeks at screening through safety follow-up, assessed up to 24 months on average4
Concentration of 2-HG in brain tumor tissue
Brain tumor tissue will be obtained from suitable patients for determination concentration of 2-HG.
Time frame
PK/PD weeks at screening through safety follow-up, assessed up to 24 months on averageOther outcomes
1
Objective Response Rate (ORR)
ORR is defined as the proportion of subjects with confirmed best overall tumor response of Complete Response (CR) or Partial Response (PR) or Minor Response (MR).
Time frame
From first dose of study drug to the time of progressive disease, assessed up to 24 months on average2
Duration of response (DoR)
DoR defined as the time from the date of the first CR or PR or MR to the first date of progressive disease (PD) or death from any cause.
Time frame
From first dose of study drug to the time of disease relapse or death, whichever comes first, assessed up to 24 months on average3
Progression-free Survival (PFS)
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.
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 24 months Source ClinicalTrials.gov