NCT06387082

A Clinical Study of HMPL-506 in Patients With Hematological Malignancies

A Multicenter, Open-Label Phase I Clinical Study to Evaluate the Safety, Pharmacokinetics and Efficacy of HMPL-506 in Patients With Hematological Malignancies

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 132 (estimated)
• Sponsor: Hutchmed · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

The study is divided into 2 Phases, Dose Escalation Phase \&Dose Expansion Phase. Dose Escalation Phase: In this phase, the accelerated titration design with the modified toxicity probability interval-2 (mTPI-2) design will be used for dose escalation and determination of the Maximum tolerated dose (MTD). Approximately 30 to 38 patients with MLL-rearranged and/or NPM1-mutant relapsed/refractory Acute Myeloid Leukemia (AML) and Acute Lymphocytic Leukemia (ALL) will be enrolled in this phase. The determined starting dose of HMPL-506, i.e., 50 mg QD (orally once daily, approximately every 24 hours）, According to the Safety Monitoring Committee (SRC) safety, efficacy and PK/PD data of the first 4 patients in the 50 mg QD dose group of HMPL-506, it was decided to administer the pre dose + therapeutic dose, initially set the pre dose for one week (or duration based on SRC decision), and then continue the treatment at the therapeutic dose. The Pre-dose is initially set as 25 mg QD (or the lead dose selected according to SRC decision), The preliminary set escalation gradient includes: a. QD dosing: 50 mg, 100 mg, 150 mg, 200 mg, 300 mg, 400 mg, etc.; b. BID dosing: starting dose of 25 mg, 50 mg, 75 mg, 100 mg, 150 mg, 200 mg, etc.; or refer to the SRC-determined incremental gradient. According to the Safety Monitoring Committee (SRC) safety, efficacy and PK/PD data of the first 4 patients in the 50 mg QD dose group of HMPL-506, it was decided to administer the lead dose + therapeutic dose, initially set the lead dose for one week (or duration based on SRC decision), and then continue the treatment at the therapeutic dose. The dose will be escalated based on available efficacy and safety data in conjunction with preclinical pharmacodynamics, PK data. safety review committee（SRC） meetings will be held to discuss the necessity of expanding the sample size of 1 or more selected dose groups, with approximately 6 to 10 patients in each dose group, to obtain a sufficient amount of safety and efficacy data. Dose Expansion Phase: The dose expansion phase will be conducted after the determination of the recommended phase 2 dose(RP2D) and/or Maximum tolerated dose （MTD） and approximately 30 to 60 patients with hematological malignancies will be enrolled to further evaluate the safety, tolerability and preliminary efficacy of HMPL-506. Patients enrolled in this phase will be divided into three cohorts: * MLL-rearranged and/or NPM1-mutant relapsed/refractory AML * MLL-rearranged relapsed/refractory ALL * Relapsed/refractory multiple myeloma (MM), and AML with genetic alterations such as NUP214 or NUP98 fusion Approximately 10 to 20 patients are planned to be enrolled in each cohort. Enrolled patients will receive oral dose of HMPL-506 at the RP2D in 28-day cycles until disease progression/relapse (except for patients who are assessed by the investigator as continuing receiving benefit from treatment with the investigational product), death, intolerable toxicity, receiving another anti-tumor therapy, failure to further benefit from the treatment as judged by the investigator, patient withdrawal, loss to follow-up or end of the study, whichever comes first.

Conditions

• Hematological Malignancies

Interventions

Type	Name	Description
DRUG	HMPL-506	HMPL-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.

Timeline

• Start date: 2024-05-27
• Primary completion: 2027-10-08
• Completion: 2027-12-08
• First posted: 2024-04-26
• Last updated: 2025-09-29

Locations

16 sites across 1 country: China