Brief Title
HMPL-760 Safety and Tolerability Study in Patients With Previously Treated CLL/SLL or NHL
Official Title
A Multicenter, Open-label, Phase 1 Study Evaluating the Safety and Tolerability of HMPL-760 in Patients With Previously Treated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) or Other Non-Hodgkin Lymphoma (NHL)
Brief Summary
An open label single-arm clinical trial to evaluate the safety, tolerability, PK, PD, and
preliminary efficacy of HMPL-760 in patients with previously treated CLL/SLL or NHL
Detailed Description
HMPL-760 is a highly potent, selective, and reversible inhibitor against BTK, which would be
studied in B-cell malignancy carrying either BTK(WT) or BTK(C481S).
This is a phase 1, open-label, multicenter, single-arm study to evaluate safety,
tolerability, PK, PD, and preliminary efficacy of HMPL-760 in patients with previously
treated CLL/SLL or NHL
The study consists of 2 parts:
Part 1- Dose Escalation to determine MTD and/or RP2D of HMPL-760
Part 2- Dose Expansion to characterize the safety and tolerability of HMPL-760
Study Phase
Phase 1
Study Type
Interventional
Primary Outcome
Incidence of DLTs
Secondary Outcome
Objective Response Rate (ORR)
Condition
CLL/SLL
Intervention
HMPL-760
Study Arms / Comparison Groups
Treatment
Description: All patients to receive HMPL-760 daily.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
0
Start Date
February 15, 2022
Completion Date
November 16, 2022
Primary Completion Date
November 16, 2022
Eligibility Criteria
Inclusion Criteria:
- ECOG performance status of 0 or 1;
- Histologically confirmed NHL or CLL with disease progression or intolerance to either
≥2 prior regimens. Patients with CLL/SLL and indolent NHL must meet criteria for
systemic therapy. Patients with gastric extranodal MZL who are H. pylori positive must
have failed H. pylori eradication therapy.
- Availability of tumor sample: This may be an archival tissue sample obtained after
most recent therapy or a fresh biopsy; if tumor sample is not available for patients
in dose escalation, the Sponsor may waive the requirement after discussion.
- Dose expansion stage only: Patients must have been treated with 1 prior regimen
containing a BTK inhibitor in cohorts 1 to 5;
- Expected survival of more than 24 weeks as determined by the Investigator.
Exclusion Criteria:
- Patients with primary central nervous system lymphoma.
- Any of the following laboratory abnormalities:
- Absolute neutrophil count (ANC) <0.75×109/L
- Hemoglobin <8 mg/L
- Platelets <50×109/L
- Note: In the dose expansion stage, patients with cell counts below the thresholds
listed above may be considered eligible if there is documented bone marrow
infiltration and Sponsor approval
- Inadequate organ function
- International normalized ratio (INR) >1.5×ULN, activated partial thromboplastin time
(aPTT) >1.5×ULN
- Patients requiring anticoagulation therapy (except vitamin K antagonists [ie,
warfarin]) but with a stable INR within the recommended range according to the local
guideline are eligible.
- Patients with presence of second primary malignant tumors within the last 2 years,
with the exception of the following:
- Basal cell carcinoma of the skin
- Squamous cell carcinoma of the skin
- Carcinoma in situ of the cervix
- Carcinoma in situ of the breast
- Clinically significant history of liver disease, including cirrhosis or current known
active infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV),
hepatitis C virus (HCV), or cytomegalovirus (CMV).
- Cancer therapy, including chemotherapy, hormonal therapy, biologic therapy, vaccine,
or radiotherapy within 3 weeks prior to initiation of study treatment. For oral
targeted therapies, a washout period of 5 half-lives of the agent (minimum 3 days)
prior to the initiation of study treatment can be used.
- Any granulocyte colony-stimulating factor treatment/blood transfusion within 7 days
before the screening hematology test.
- Prior use of any drug that is a strong inducer or inhibitor of CYP3A4 within 2 weeks
prior to initiation of study treatment.
- Prior use of proton pump inhibitors (PPIs) within 5 days of study treatment
- Any transplant within 100 days prior to initiation of study treatment
- Clinically significant active infection or with an unexplained fever.
- Treatment within a clinical study of an investigational agent or using an
investigational device within 3 weeks prior to initiation of the current study
treatment.
- AEs from prior antineoplastic therapy that have not resolved to grade <1
- Pregnant (positive urine or serum beta human chorionic gonadotropin test) or lactating
women.
- New Your Heart Association (NYHA) class II or greater congestive heart failure.
NOTE: Only key inclusion/exclusion criteria are listed. Full details are in the protocol.
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Vijay Jayaprakash, MBBS, PHD, ,
Location Countries
Australia
Location Countries
Australia
Administrative Informations
NCT ID
NCT05176691
Organization ID
2021-760-GLOB1
Responsible Party
Sponsor
Study Sponsor
Hutchmed
Study Sponsor
Vijay Jayaprakash, MBBS, PHD, Study Director, Hutchison Medipharma Limited
Verification Date
February 2023