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

Hematological Malignancies Clinical Trial

Official title: 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

Clinical Trial 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 98 patients, including approximately 30 to 38 patients in the dose escalation phase and approximately 30 to 60 patients in the dose expansion phase.

Clinical Trial 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）, will be subsequently escalated to 100 mg QD (100%), 200 mg QD (100%), 300 mg QD (50%), and finally 400 mg QD (33%) (this is an assumed dose gradient, and the percentage in brackets corresponds to the dose increment from the previous dose level). A modified Fibonacci design will be used for dose escalation.

The dose will be escalated based on available efficacy and safety data in conjunction with preclinical pharmacodynamics, PK data. safety review committees（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. In addition, the SRC will determine the necessity of exploring a dose above 400 mg QD or an intermediate dose between two dose groups or other administration methods.

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. ;

Related Conditions & MeSH terms

• Hematologic Neoplasms
• Hematological Malignancies
• Neoplasms

• NCT number: NCT06387082
• Study type: Interventional
• Source: Hutchmed
• Contact: Jian Chen, Doctor
• Phone: +86 21 2067 1942
• Email: jianc2@hutch-med.com
• Status: Recruiting
• Phase: Phase 1
• Start date: May 27, 2024
• Completion date: December 8, 2027