A Clinical Study of HMPL-506 in Patients With Hematological Malignancies
ConditionHematological Malignancies
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorHutchmed
About this trial
This is a Phase 1, multicenter, open-label clinical study of HMPL-506 administered orally in the treatment of hematological malignancies. Only eligible patients who provide the signed informed consent form (ICF) can be enrolled in this study. The study consists of two phases, i.e., a dose escalation phase and a dose expansion phase. The study is expected to enroll approximately 60 to 132 patients, including approximately 30 to 38 patients in the dose escalation phase and approximately 30 to 72 patients in the dose expansion phase.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Subjects must meet all of the following criteria to be eligible for enrolment.
Having understood this study adequately and being voluntary to sign the ICF;
Age ≥18 years;
1) Dose escalation phase: patient with MLL-rearranged and/or NPM1-mutant relapsed/refractory AML or ALL (confirmed as per the 2022 World Health Organization (WHO) Classification of Myeloid Neoplasms and Acute Leukemia): 2) Dose expansion phase: approximately 10 to 20 patients will be enrolled in each of the following cohorts
Disqualifiers
Patients who have previously received treatment with menin inhibitors and experienced progression during treatment;
Patients with definite active central nervous system (CNS) leukemia (prior CNS leukemia has been treated and controlled, but a cerebrospinal fluid test through lumbar puncture is required at screening to confirm the absence of CNS involvement);
ALT or AST > 3 × ULN in the absence of liver involvement with leukemia or ALT or AST > 5 × ULN in the presence of liver involvement with leukemia (the latter criterion is not applicable in the dose escalation phase);
Glomerular filtration rate or creatinine clearance estimated using Cockcroft-Gault formula < 50 mL/min.
Trial design
Design model
Sequential
Treatments tested in this trial
HMPL-506
DrugHMPL-506 will be administered orally in 28-day cycles, until disease progression/relapse , death, intolerable toxicity, receipt of another anti-tumor therapy (including HSCT), failure to further benefit , patient withdrawal, loss to follow-up or end of the study, whichever comes first.
Treatment groups
132 Participants
are divided into 13 treatment groups13
Treatment groupsSee each treatment group below.
Group A: 50mg QDExperimental treatment 1 intervention
Group B: 100mg QDExperimental treatment 1 intervention
Group C: 200mg QDExperimental treatment 1 intervention
Group D: 300mg QDExperimental treatment 1 intervention
Group E: 400mg QDExperimental treatment 1 intervention
Group F: 25 mg BIDExperimental treatment 1 intervention
Group G: 50mg BIDExperimental treatment 1 intervention
Group H: 75 mg BIDExperimental treatment 1 intervention
Group I: 150mg QDExperimental treatment 1 intervention
Group J: 100mg BIDExperimental treatment 1 intervention
Group K: 150mg BIDExperimental treatment 1 intervention
Group L: 200mg BIDExperimental treatment 1 intervention
Group M: Other dose determined by SRCExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Safety evaluation: Safety Incidence of Dose-limiting Toxicity (DLTs)
Incidence of serious Dose-limiting Toxicity evaluated using the NCI CTCAE V5.0.
Time frame
The DLT assessment window is Cycle 1 + 3 days (starting from dosing on Day -3, i.e., 28 + 3 days) in the first two dose groups (50 mg and 100 mg), and Cycle 1 (starting from Day 1 of each cycle, i.e., 28 days) in other dose groups.2
Safety evaluation: Incidence of serious adverse events (SAEs) and Relationship to Study Drug
Incidence of serious adverse events (SAEs) evaluated using the NCI CTCAE V5.0 and the relationship of DLTs and SAEs with the investigational product. The assessment window is from the first dose of HMPL-506 to 30 days after last dose, or initiation of a new anti-tumor therapy, whichever comes first.
Time frame
The time from the first dose of HMPL-506 to 30 days after last dose, or initiation of a new anti-tumor therapy, whichever comes first. Maybe assessed up to 42 months3
Efficacy evaluation: Anti-tumor efficacy evaluation.
Performing anti-tumor efficacy evaluation of HMPL-506 based on Complete response (CR), Complete response with partial recovery of hematology (CRh), Complete response with incomplete hematological recovery (CRi) assessed by the Investigator. Response evaluation in AML will be conducted based on the European LeukmiaNet (ELN) 2022 criteria; response evaluation in ALL will be conducted based on the National Comprehensive Cancer Network (NCCN) Guidelines for the Diagnosis and Treatment of ALL (2023 Version 3).
Time frame
To assess at every cycle during the first 6 cycles of treatment (each cycle is 28 days) and once every 2 cycles thereafter; response evaluation will also be conducted at each Event-free survival (EFS) follow-up visit.Maybe assessed up to 42 Months.Secondary outcomes
1
Incidence of adverse events (AEs) and Relationship to Study Drug
Incidence of each type of adverse event evaluated by NCI CTCAE V5.0 and its relationship to study drug
Time frame
The time from the first dose of HMPL-506 to 30 days after last dose, or initiation of a new anti-tumor therapy, whichever comes first. Maybe assessed up to 42 Months.2
Adverse Events Associated with Dose Modifications
Incidence of adverse events leading to dose interruption, reduction, or treatment discontinuation
Time frame
The time from the first dose of HMPL-506 to 30 days after last dose, or initiation of a new anti-tumor therapy, whichever comes first. Maybe assessed up to 42 Months.3
Evaluate electrocardiogram (ECG) assessments.
Observe QT interval changes before and after treatment.
Time frame
The time from the first dose of HMPL-506 to 30 days after last dose, or initiation of a new anti-tumor therapy, whichever comes first. Maybe assessed up to 42 Months.4
Complete response rate (CR rate)
Defined as the proportion of subjects achieving CR as assessed by the investigator.Response evaluation in AML will be conducted based on the European LeukmiaNet (ELN) 2022 criteria; response evaluation in ALL will be conducted based on the National Comprehensive Cancer Network (NCCN) Guidelines for the Diagnosis and Treatment of ALL (2023 Version 3).
Time frame
To assess at every cycle during the first 6 cycles of treatment (each cycle is 28 days) and once every 2 cycles thereafter; response evaluation will also be conducted at each EFS follow-up visit.Maybe assessed up to 42 Months.Other outcomes
1
Evaluate the changes of the Pharmacodynamic Biomarker
Changes in Pharmacodynamic biomarkers (e.g., MEIS3, HOXA9, CD11b etc.) before and after HMPL506 administration, and correlations with dosing and efficacy
Time frame
the time before the first dose of HMPL-506 to 30 days after last dose or Disease progression.Maybe assessed up to 42 Months. Source ClinicalTrials.gov