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

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.