hmpl-760 safety and tolerability study in patients with previously treated cll/sll or nhl

Conditions: CLL/SLL; NHL; MCL; MZL; Lymphoplasmacytic Lymphoma; Waldenstrom Macroglobulinemia; Follicular Lymphoma; DLBCL; Richter Syndrome

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

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.

Keywords: lymphoplasmacytic lymphoma/waldenstrom's macroglobulinemia chronic lymphocytic leukemia non-hodgkin lymphoma mantle cell lymphoma marginal zone lymphoma follicular lymphoma diffuse large b-cell lymphoma btk inhibitor