Study of HS-10382 Combination in Patients With Chronic Myeloid Leukemia (CML)

Phase 1Not Yet RecruitingNCT06530810

Jiangsu Hansoh Pharmaceutical Co., Ltd.100 enrolled

Overview

HS-10382 is a small molecular, oral potent, allosteric inhibitor. By binding a myristoyl site of the BCR-ABL1 protein, HS-10382 locks BCR-ABL1 into an inactive conformation. Flumatinib is the first approved second generation TKI in China and a derivative of imatinib. The primary objective of this study is to evaluation the safety and tolerability and of HS-10382 combination therapy in patients with chronic myeloid leukemia (CML). The secondary objectives is to evaluate the PK profile, major metabolites and efficacy of HS-10382 in CML-CP/AP subjects after combination therapy, and to explore the kinase domain mutations associated with TKI resistance

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

100

Conditions

Chronic Myelogenous Leukemia CML Chronic Phase CML Accelerated Phase

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Signed informed consent form. * Men or women aged more than or equal to (≥) 18 years, and less than (\<) 75 years. * CML-CP/AP patients with the Ph chromosome or BCR-ABL1 fusion genes. * Patient with CML-CP/AP who are resistant to or intolerant to previous TKIs therapy. * ECOG performance status of 0-1 and no worsening within 2 weeks before the first dose. * Life expectancy ≥ 12 weeks. * Men or women should be using adequate contraceptive measures throughout the study; Females should not be breastfeeding at the time of screening, during the study and until 6 months after completion of the study. * Females must have evidence of non-childbearing potential. Exclusion Criteria: * CML-CP patients who have acquired CCyR and have not lost it. * Patients with CML-CP who have progressed to AP or blast phase(BP.) * Patients with CML-AP who have obtained CHR or no evidence of CML in peripheral blood. * Patients with CML-AP who have progressed to BP. * Previous treatment with a BCR-ABL1 TKI allosteric inhibitor . * Impaired cardiac function including any one of the following: * Resting corrected QT interval (QTc) \> 470 ms obtained from electrocardiogram (ECG), using the screening clinic's ECG machine and Fridericia's formula for QT interval correction (QTcF). * Any clinically important abnormalities in rhythm, conduction, or morphology of the resting ECG. * Any factors that increase the risk of QTc prolongation or risk of arrhythmic events, * Left ventricular ejection fraction (LVEF) ≤ 50%. * Myocardial infarction occurred within 6 months of the first scheduled dose of study drug.; * Congestive heart failure occurred within 6 months of the first scheduled dose of study drug.; * Uncontrollable angina. * History of acute pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis * Any severe or uncontrolled systemic diseases (i.e. uncontrolled hypertension or diabetes). * Clinically severe gastrointestinal dysfunction that may affect drug intake, transport or absorption. * Severe infection within 4 weeks prior to the first scheduled dose of study drug * Inadequate other organ function. * History of other malignancies. * History of hypersensitivity to any active or inactive ingredient of HS-10382 and flumatinib. * History of neuropathy or mental disorders, including epilepsy and dementia. * Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions, and requirements

Outcomes

Primary Outcomes

Maximum tolerated dose (MTD) for HS-10382 combined treatment

MTD was defined as the previous dose level at which 2 out of 3 subjects or 2 out of 6 subjects experienced a DLT

Time frame: Up to day 28 from the first dose

Secondary Outcomes

Incidence and severity of treatment-emergent adverse events

Assessed by number and severity of adverse events as recorded on the case report form, vital signs, laboratory variables, physical examination, electrocardiogram, and NCI CTCAE v5.0