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

NCT06387082 | Recruiting Phase 1

• 1 other identifier: 2023-506-00CH1
• Study Type: interventional
• Target: 132
• Locations: 1 country
• Sites: 16

Brief 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.

Conditions

Hematological Malignancies

Outcome Measures

Primary Outcomes (3)

• Safety evaluation: Safety Incidence of Dose-limiting Toxicity (DLTs)

  Incidence of serious Dose-limiting Toxicity evaluated using the NCI CTCAE V5.0.

  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.

• 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.

  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

• 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).

  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 (19)

• Incidence of adverse events (AEs) and Relationship to Study Drug

  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.

• Adverse Events Associated with Dose Modifications

  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.

• Evaluate electrocardiogram (ECG) assessments.

  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.

• Complete response rate (CR rate)

  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.

• Complete response (CR)+ Complete response with partial recovery of hematology (CRh) rate

  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

  the time before the first dose of HMPL-506 to 30 days after last dose or Disease progression.Maybe assessed up to 42 Months.

Study Arms (13)

50mg QD

EXPERIMENTAL

The starting dose of 50 mg QD will be escalated using the accelerated titration design in the first enrolled subject. If no DLT is observed and no Grade 2 or higher investigational product-related adverse events occur during the DLT observation period at the dose 50mg QD, the dose can be escalated to 100 mg QD, and the mTPI-2 design will be used for dose escalation. The dose will be escalated based on available efficacy and safety data in conjunction with preclinical Pharmacodynamics, Pharmacokinetic (PK) and Pharmacodynamics (PD) data.

Drug: HMPL-506

100mg QD

EXPERIMENTAL

At least 3 patients will be enrolled at each dose level and additional 3 patients will be recruited at the dose level decided by the next cohort following the rules specified in the protocol when all patients in the current dose group complete the DLT assessment. The number of patients finally enrolled in each dose group is not limited to 3 patients, and the need to increase the number of patients may be decided by the sponsor or by discussion at a SRC meeting to obtain the relevant data required. However, at least 3 DLT evaluable patients per dose group must be ensured.

Drug: HMPL-506

200mg QD

EXPERIMENTAL

At least 3 patients will be enrolled at each dose level and additional 3 patients will be recruited at the dose level decided by the next cohort following the rules specified in the protocol when all patients in the current dose group complete the DLT assessment. The number of patients finally enrolled in each dose group is not limited to 3 patients, and the need to increase the number of patients may be decided by the sponsor or by discussion at a SRC meeting to obtain the relevant data required. However, at least 3 DLT evaluable patients per dose group must be ensured.

Drug: HMPL-506

300mg QD

EXPERIMENTAL

At least 3 patients will be enrolled at each dose level and additional 3 patients will be recruited at the dose level decided by the next cohort following the rules specified in the protocol when all patients in the current dose group complete the DLT assessment. The number of patients finally enrolled in each dose group is not limited to 3 patients, and the need to increase the number of patients may be decided by the sponsor or by discussion at a SRC meeting to obtain the relevant data required. However, at least 3 DLT evaluable patients per dose group must be ensured.

Drug: HMPL-506

400mg QD

EXPERIMENTAL

At least 3 patients will be enrolled at each dose level and additional 3 patients will be recruited at the dose level decided by the next cohort following the rules specified in the protocol when all patients in the current dose group complete the DLT assessment. The number of patients finally enrolled in each dose group is not limited to 3 patients, and the need to increase the number of patients may be decided by the sponsor or by discussion at a SRC meeting to obtain the relevant data required. However, at least 3 DLT evaluable patients per dose group must be ensured.

Drug: HMPL-506

25 mg BID

EXPERIMENTAL

At least 3 patients will be enrolled at each dose level and additional 3 patients will be recruited at the dose level decided by the next cohort following the rules specified in the protocol when all patients in the current dose group complete the DLT assessment. The number of patients finally enrolled in each dose group is not limited to 3 patients, and the need to increase the number of patients may be decided by the sponsor or by discussion at a SRC meeting to obtain the relevant data required. However, at least 3 DLT evaluable patients per dose group must be ensured.

Drug: HMPL-506

50mg BID

EXPERIMENTAL

At least 3 patients will be enrolled at each dose level and additional 3 patients will be recruited at the dose level decided by the next cohort following the rules specified in the protocol when all patients in the current dose group complete the DLT assessment. The number of patients finally enrolled in each dose group is not limited to 3 patients, and the need to increase the number of patients may be decided by the sponsor or by discussion at a SRC meeting to obtain the relevant data required. However, at least 3 DLT evaluable patients per dose group must be ensured.

Drug: HMPL-506

75 mg BID

EXPERIMENTAL

At least 3 patients will be enrolled at each dose level and additional 3 patients will be recruited at the dose level decided by the next cohort following the rules specified in the protocol when all patients in the current dose group complete the DLT assessment. The number of patients finally enrolled in each dose group is not limited to 3 patients, and the need to increase the number of patients may be decided by the sponsor or by discussion at a SRC meeting to obtain the relevant data required. However, at least 3 DLT evaluable patients per dose group must be ensured.

Drug: HMPL-506

150mg QD

EXPERIMENTAL

At least 3 patients will be enrolled at each dose level and additional 3 patients will be recruited at the dose level decided by the next cohort following the rules specified in the protocol when all patients in the current dose group complete the DLT assessment. The number of patients finally enrolled in each dose group is not limited to 3 patients, and the need to increase the number of patients may be decided by the sponsor or by discussion at a SRC meeting to obtain the relevant data required. However, at least 3 DLT evaluable patients per dose group must be ensured.

Drug: HMPL-506

100mg BID

EXPERIMENTAL

At least 3 patients will be enrolled at each dose level and additional 3 patients will be recruited at the dose level decided by the next cohort following the rules specified in the protocol when all patients in the current dose group complete the DLT assessment. The number of patients finally enrolled in each dose group is not limited to 3 patients, and the need to increase the number of patients may be decided by the sponsor or by discussion at a SRC meeting to obtain the relevant data required. However, at least 3 DLT evaluable patients per dose group must be ensured.

Drug: HMPL-506

150mg BID

EXPERIMENTAL

At least 3 patients will be enrolled at each dose level and additional 3 patients will be recruited at the dose level decided by the next cohort following the rules specified in the protocol when all patients in the current dose group complete the DLT assessment. The number of patients finally enrolled in each dose group is not limited to 3 patients, and the need to increase the number of patients may be decided by the sponsor or by discussion at a SRC meeting to obtain the relevant data required. However, at least 3 DLT evaluable patients per dose group must be ensured.

Drug: HMPL-506

200mg BID

EXPERIMENTAL

At least 3 patients will be enrolled at each dose level and additional 3 patients will be recruited at the dose level decided by the next cohort following the rules specified in the protocol when all patients in the current dose group complete the DLT assessment. The number of patients finally enrolled in each dose group is not limited to 3 patients, and the need to increase the number of patients may be decided by the sponsor or by discussion at a SRC meeting to obtain the relevant data required. However, at least 3 DLT evaluable patients per dose group must be ensured.

Drug: HMPL-506

Other dose determined by SRC

EXPERIMENTAL

At least 3 patients will be enrolled at each dose level and additional 3 patients will be recruited at the dose level decided by the next cohort following the rules specified in the protocol when all patients in the current dose group complete the DLT assessment. The number of patients finally enrolled in each dose group is not limited to 3 patients, and the need to increase the number of patients may be decided by the sponsor or by discussion at a SRC meeting to obtain the relevant data required. However, at least 3 DLT evaluable patients per dose group must be ensured.

Drug: HMPL-506

Interventions

HMPL-506 DRUG

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.

Also known as: Two strengths of HMPL-506 tablets (25 mg and 100 mg) will be used for this clinical study

100mg BID; 100mg QD; 150mg BID; 150mg QD; 200mg BID; 200mg QD; 25 mg BID; 300mg QD; 400mg QD; 50mg BID; 50mg QD; 75 mg BID; Other dose determined by SRC

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• \) 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
• MLL-rearranged and/or NPM1-mutant relapsed/refractory AML
• MLL-rearranged relapsed/refractory ALL
• Relapsed/refractory MM (which can be screened and enrolled without biomarker testing), and AML harboring genetic alterations such as NUP214 or NUP98 fusion
• Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to 2;
• Agree to undergo bone marrow aspiration and/or biopsy before and during treatment;
• Women patients of childbearing potential must agree to use highly effective contraceptive methods from screening until 30 days after discontinuation of study treatment, and their male partners must use condoms. See Appendix 11 (Definition of Women of Childbearing Potential \[WOCBP\] and Acceptable and Unacceptable Contraceptive Methods) for more details. And women patients of childbearing potential should agree not to donate eggs (or oocytes) for reproductive purposes during this period.
• Male patients with a female partner of childbearing potential must agree to use condoms when having intercourse during the study and within 30 days after discontinuation of the investigational product. Patients should avoid sperm donation or freezing of sperm during the study and within 30 days after discontinuation of the investigational product.

You may not qualify if:

• Subjects will be excluded from this study project if they meet any of the following criteria:
• 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);
• Serum total bilirubin (TBIL) \> 1.5 × the upper limit of normal (ULN), with the exception of the following patients:
• Patients with Gilbert's disease, with normal alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and serum TBIL ≤ 3 × ULN
• 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.
• International normalized ratio (INR) \> 1.5 × ULN or activated partial thromboplastin time (aPTT) \> 1.5 × ULN; this criterion is not applicable in patients who are receiving anticoagulant therapy.
• Known history of clinically significant liver disease, including viral hepatitis or other types of hepatitis:
• Patients with hepatitis B (HBV) (HBsAg or HBcAb positive) can be enrolled if they test negative for HBV DNA by PCR, but the HBV DNA test should be performed every cycle
• Patients with hepatitis C (HCV) can be enrolled if they test negative for HCV RNA by PCR.
• Known human immunodeficiency virus (HIV) infection.
• Women who are pregnant (with a positive pregnancy test before administration) or breastfeeding.
• History of stroke or intracranial hemorrhage within 6 months prior to the first dose of the investigational product.
• Patients with other primary malignancies within the last 5 years, but patients with the following non-invasive tumors that have been treated with curative intent are exceptions: basal cell carcinoma of skin, squamous cell carcinoma of skin, in situ carcinoma of cervix and breast cancer in situ.

Sponsors & Collaborators

• Hutchmed: lead

Study Sites (16)

Xiangya Hospital of Central South University

Changsha, China

RECRUITING

First Affiliated Hospital of Chongqing Medical University

Chongqing, China

RECRUITING

Fujian Medical University Union Hospital

Fuzhou, China

NOT YET RECRUITING

Nanfang Hospital, Southern Medical University

Guangzhou, China

RECRUITING

Sun Yat-sen University Cancer Center

Guangzhou, China

NOT YET RECRUITING

The Affiliated Hospital of Guizhou Medical University

Guiyang, China

NOT YET RECRUITING

The First Affiliated Hospital, Zhejiang University

Hangzhou, China

RECRUITING

Anhui Provincial Hospital

Hefei, China

RECRUITING

Qilu Hospital of Shandong University

Jinan, China

RECRUITING

The First Affiliated Hospital with Nanjing Medical University

Nanjing, China

RECRUITING

Shengjing Hospital of China Medical University

Shenyang, China

RECRUITING

The First Affiliated Hospital of Soochow University

Suzhou, China

RECRUITING

Blood Diseases Hospital, Chinese Academy of medical Sciences

Tianjin, China

RECRUITING

Tianjin People's Hospital

Tianjin, China

RECRUITING

Wuhan Union Hospital of China

Wuhan, China

RECRUITING

Henan Cancer Hospital

Zhengzhou, China

RECRUITING

MeSH Terms

Conditions

Hematologic Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Jianxiang Wang, Master

  Blood Diseases Hospital, Chinese Academy of medical Sciences

  PRINCIPAL INVESTIGATOR

• Hui Wei, Master

  Blood Diseases Hospital, Chinese Academy of medical Sciences

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Erin Lou, Doctor

CONTACT

+86 21 2067 1942; erinl@hutch-med.com

Panfeng Tan, Doctor

CONTACT

+86 21 2067 1828; panfengt@hutch-med.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 19, 2024
• First Posted: April 26, 2024
• Study Start: May 27, 2024
• Primary Completion (Estimated): October 8, 2027
• Study Completion (Estimated): December 8, 2027
• Last Updated: September 29, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (16)