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

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)

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

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

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.