Investigating HS-10382 for Chronic Myeloid Leukemia

A Phase I, Open-label, Multicenter Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Efficacy of Single and Multiple Doses of Oral Administration of HS-10382 in Patients With Chronic Myeloid Leukemia.

This study is testing a new oral medication called HS-10382 to see if it can help people with chronic myeloid leukemia who have certain genetic mutations or haven't responded to other treatments.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 108 (estimated)
• Ages: 18 Years to 74 Years
• Sex: All
• Sponsor: Jiangsu Hansoh Pharmaceutical Co., Ltd. (Industry-sponsored)
• Locations: 1 site (Wuhan, Hubei)
• Trial ID: NCT05367700 on ClinicalTrials.gov

What this trial studies

This study evaluates HS-10382, an oral allosteric inhibitor, in patients with chronic myeloid leukemia (CML) who have either the T315I mutation or are resistant to previous treatments. It is an open-label, multicenter, dose-escalation and expansion study designed to assess the safety, tolerability, pharmacokinetics, and preliminary anti-CML activity of HS-10382. The study consists of two parts: a dose escalation phase to determine the maximum tolerated dose and a dose expansion phase to further evaluate efficacy and safety. Participants will be monitored for adverse events throughout the treatment and for 28 days post-treatment.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 to 75 with chronic or accelerated phase CML who are resistant to or intolerant of previous BCR-ABL1 TKI therapies.

Not a fit: Patients who have not lost their complete cytogenetic response or have progressed to blast phase CML may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with CML who have not responded to existing therapies.

How similar studies have performed: While this approach is novel, other studies have shown promise with allosteric inhibitors in targeting BCR-ABL1 mutations.

Eligibility criteria

Inclusion Criteria:

1. Signed informed consent form.
2. Men or women aged more than or equal to (≥) 18 years, and less than (\<) 75 years.
3. CML-CP/AP patients with the Ph chromosome or BCR-ABL1 fusion genes.
4. Patient with CML-CP/AP who are resistant to or intolerant to previous TKIs therapy.
5. ECOG performance status of 0-2.
6. Life expectancy ≥ 12 weeks.
7. 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.
8. Females must have evidence of non-childbearing potential.

Exclusion Criteria:

1. CML-CP patients who have acquired CCyR and have not lost it.
2. Patients with CML-CP who have progressed to AP or blast phase(BP.)
3. Patients with CML-AP who have obtained CHR or no evidence of CML in peripheral blood.
4. Patients with CML-AP who have progressed to BP.
5. Previous treatment with a BCR-ABL1 TKI allosteric inhibitor .
6. Impaired cardiac function including any one of the following:

   1. 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).
   2. Any clinically important abnormalities in rhythm, conduction, or morphology of the resting ECG.
   3. Any factors that increase the risk of QTc prolongation or risk of arrhythmic events,
   4. Left ventricular ejection fraction (LVEF) ≤ 50%.
   5. During screening period, ECG examination showed average heart rate \<50 beats per minute.
   6. Myocardial infarction occurred within 6 months of the first scheduled dose of HS-10382.;
   7. Congestive heart failure occurred within 6 months of the first scheduled dose of HS-10382.;
   8. Uncontrollable angina.
7. History of acute pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis
8. Any severe or uncontrolled systemic diseases (i.e. uncontrolled hypertension or diabetes).
9. Clinically severe gastrointestinal dysfunction that may affect drug intake, transport or absorption.
10. Severe infection within 4 weeks prior to the first scheduled dose of HS-10382.
11. History of significant congenital or acquired bleeding disorders unrelated to CML.
12. Inadequate other organ function.
13. History of other malignancies.
14. History of hypersensitivity to any active or inactive ingredient of HS-10382.
15. History of neuropathy or mental disorders, including epilepsy and dementia.
16. 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.

Where this trial is running

Wuhan, Hubei

• Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology — Wuhan, Hubei, China (Recruiting)

Study contacts

• Principal investigator: Yu Hu — Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
• Study coordinator: Yu Hu

Conditions CML, Chronic Phase; CML, Accelerated Phase; CML-CP/AP; HS-10382; BCR-ABL TKI; Phase I; Allosteric inhibitor