HMPL-760 Safety and Tolerability Study in Patients With Previously Treated CLL/SLL or NHL

HUTCHMED

Status and phase

Withdrawn

Phase 1

Conditions

CLL/SLL

Waldenstrom Macroglobulinemia

MCL

NHL

Follicular Lymphoma

DLBCL

Lymphoplasmacytic Lymphoma

Richter Syndrome

MZL

Treatments

Drug: HMPL-760

Study type

Interventional

Funder types

Industry

Identifiers

NCT05176691

2021-760-GLOB1

Details and patient eligibility

About

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

Full 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

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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.