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

NCT ID: NCT06387082

Last Updated: 2025-09-29

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 132 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-05-27
• Study Completion Date: 2027-12-08

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.

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

50mg QD

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.

Group Type: EXPERIMENTAL

HMPL-506

Intervention Type: 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.

100mg QD

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.

Group Type: EXPERIMENTAL

HMPL-506

Intervention Type: 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.

200mg QD

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.

Group Type: EXPERIMENTAL

HMPL-506

Intervention Type: 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.

300mg QD

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.

Group Type: EXPERIMENTAL

HMPL-506

Intervention Type: 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.

400mg QD

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.

Group Type: EXPERIMENTAL

HMPL-506

Intervention Type: 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.

25 mg BID

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.

Group Type: EXPERIMENTAL

HMPL-506

Intervention Type: 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.

50mg BID

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.

Group Type: EXPERIMENTAL

HMPL-506

Intervention Type: 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.

75 mg BID

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.

Group Type: EXPERIMENTAL

HMPL-506

Intervention Type: 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.

150mg QD

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.

Group Type: EXPERIMENTAL

HMPL-506

Intervention Type: 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.

100mg BID

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.

Group Type: EXPERIMENTAL

HMPL-506

Intervention Type: 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.

150mg BID

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.

Group Type: EXPERIMENTAL

HMPL-506

Intervention Type: 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.

200mg BID

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.

Group Type: EXPERIMENTAL

HMPL-506

Intervention Type: 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.

Other dose determined by SRC

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.

Group Type: EXPERIMENTAL

HMPL-506

Intervention Type: 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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

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

Eligibility Criteria

Inclusion Criteria

• Subjects must meet all of the following criteria to be eligible for enrolment.

1. Having understood this study adequately and being voluntary to sign the ICF;

2. Age ≥18 years;

3. 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

• 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

4. Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to 2;

5. Agree to undergo bone marrow aspiration and/or biopsy before and during treatment;

6. 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.

7. 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.

Exclusion Criteria

• Subjects will be excluded from this study project if they meet any of the following criteria:

1. Patients who have previously received treatment with menin inhibitors and experienced progression during treatment;

2. 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);

3. 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

4. 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);

5. Glomerular filtration rate or creatinine clearance estimated using Cockcroft-Gault formula < 50 mL/min.

6. 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.

7. 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.

8. Known human immunodeficiency virus (HIV) infection.

9. Women who are pregnant (with a positive pregnancy test before administration) or breastfeeding.

10. History of stroke or intracranial hemorrhage within 6 months prior to the first dose of the investigational product.

11. 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.

12. Patients who meet any of the following cardiac function-related criteria:

• Any clinically significant abnormal heart rhythm or conduction requiring clinical intervention.
• Hereditary long QT syndrome or QTcF > 470 msec.
• Clinically significant cardiovascular diseases, including acute myocardial infarction, unstable angina pectoris, coronary artery bypass grafting within 6 months prior to enrollment, New York Heart Association (NYHA) Class III or above congestive heart failure, left ventricular ejection fraction (LVEF) < 50%, or uncontrolled hypertension (systolic blood pressure > 140 mmHg or diastolic blood pressure > 90 mmHg), or mean heart rate > 100 beats/min on triplicate electrocardiograms (ECGs) at screening.

13. Receipt of systemic anti-tumor therapy or radiotherapy within 2 weeks prior to initiation of study treatment:

• For patients with increased peripheral white blood cell count (WBC > 25 × 109/L), use of hydroxycarbamide is allowed to control peripheral WBC before enrollment and during HMPL-506 treatment.
• Prophylactic intrathecal injection of chemotherapy drugs (cytarabine, dexamethasone and methotrexate) to prevent CNS leukemia is allowed.

14. Patients who have received HSCT within 60 days before initiation of study treatment, or are receiving immunosuppressive therapy after HSCT at screening, or require medical intervention to control graft versus host disease (GVHD):

• Patients who use fixed-dose oral glucocorticoids and/or topical glucocorticoids for the treatment of skin GVHD can be enrolled.

15. Patients who have received treatment with herbal and traditional medicines/their active ingredients with definite anti-tumor activity within 1 week before initiation of study treatment.

16. Use of potent inducers or inhibitors of CYP3A4 within 2 weeks (3 weeks for St John's wort) or 5 half-lives (whichever is longer) before initiation of study treatment.

17. An interval of less than 2 weeks from the last dose of any small molecular drug or of less than 4 weeks from the last dose of any macromolecular drug (e.g., antibody drugs) administered during previous participation in other drug clinical trials before treatment initiation in this study.

18. Patients who have undergone major surgery within 4 weeks prior to the first dose of the investigational product.

19. Toxicities from previous anti-tumor treatments have not yet recovered to Grade ≤ 1 (excluding alopecia).

20. Patients with uncontrolled active infection requiring hospitalization or intravenous antibiotics (defined as persistent signs/symptoms related to the infection without improvement despite receipt of appropriate anti-infection therapy and/or other treatments); or unexplained pyrexia with a temperature above 38.5℃ during the screening period (only patients with tumor fever as judged by the investigator can be enrolled);

• Patients with neutropenia who, in the opinion of the investigator, require prophylactic intravenous antibiotics can be enrolled

21. Presence of conditions that may affect the absorption of the investigational product as judged by the investigator, such as inability to take drugs orally, past surgery history or severe gastrointestinal diseases including dysphagia and active gastric ulcer.

22. Patients with poor compliance who are judged by the investigator as not suitable for participation in this clinical study.

23. Any other disease, metabolic abnormality, physical examination abnormality or clinically significant laboratory test abnormality, based on which the investigator has reason to suspect that the patient has certain disease or condition that is not suitable for treatment with the investigational product, or that will affect the interpretation of study results or will put the patient at high risk.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hutchmed

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jianxiang Wang, Master

Role: PRINCIPAL_INVESTIGATOR

Blood Diseases Hospital, Chinese Academy of medical Sciences

Hui Wei, Master

Role: PRINCIPAL_INVESTIGATOR

Blood Diseases Hospital, Chinese Academy of medical Sciences

Locations

Xiangya Hospital of Central South University

Changsha, , China

Site Status: RECRUITING

First Affiliated Hospital of Chongqing Medical University

Chongqing, , China

Site Status: RECRUITING

Fujian Medical University Union Hospital

Fuzhou, , China

Site Status: NOT_YET_RECRUITING

Nanfang Hospital, Southern Medical University

Guangzhou, , China

Site Status: RECRUITING

Sun Yat-sen University Cancer Center

Guangzhou, , China

Site Status: NOT_YET_RECRUITING

The Affiliated Hospital of Guizhou Medical University

Guiyang, , China

Site Status: NOT_YET_RECRUITING

The First Affiliated Hospital, Zhejiang University

Hangzhou, , China

Site Status: RECRUITING

Anhui Provincial Hospital

Hefei, , China

Site Status: RECRUITING

Qilu Hospital of Shandong University

Jinan, , China

Site Status: RECRUITING

The First Affiliated Hospital with Nanjing Medical University

Nanjing, , China

Site Status: RECRUITING

Shengjing Hospital of China Medical University

Shenyang, , China

Site Status: RECRUITING

The First Affiliated Hospital of Soochow University

Suzhou, , China

Site Status: RECRUITING

Blood Diseases Hospital, Chinese Academy of medical Sciences

Tianjin, , China

Site Status: RECRUITING

Tianjin People's Hospital

Tianjin, , China

Site Status: RECRUITING

Wuhan Union Hospital of China

Wuhan, , China

Site Status: RECRUITING

Henan Cancer Hospital

Zhengzhou, , China

Site Status: RECRUITING

Countries

China

Central Contacts

Erin Lou, Doctor

Role: CONTACT

erinl@hutch-med.com

+86 21 2067 1942

Panfeng Tan, Doctor

Role: CONTACT

panfengt@hutch-med.com

+86 21 2067 1828 ext. 5934

Facility Contacts

Yajing Xu

Role: primary

Lin Liu

Role: primary

Shaoyuan Wang

Role: primary

Yu Zhang

Role: primary

Yang Liang

Role: primary

Jishi Wang

Role: primary

Jie Jin

Role: primary

Xiaoyu Zhu

Role: primary

Chunyan Ji

Role: primary

Yu Zhu

Role: primary

Wei Yang

Role: primary

Suning Chen

Role: primary

Mingyuan Sun

Role: primary

Xingli Zhao

Role: primary

Min Zhang

Role: primary

Xudong Wei

Role: primary

Other Identifiers

2023-506-00CH1

Identifier Type: -

Identifier Source: org_study_id