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)
Overview
- Phase
- Phase 1
- Intervention
- HMPL-760
- Conditions
- CLL/SLL
- Sponsor
- Hutchmed
- Locations
- 35
- Primary Endpoint
- MTD
- Status
- Withdrawn
- Last Updated
- 3 years ago
Overview
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
Investigators
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:
Arms & Interventions
Treatment
All patients to receive HMPL-760 daily.
Intervention: HMPL-760
Outcomes
Primary Outcomes
MTD
Time Frame: From 1st dose to within 30 days of last dose
To evaluate maximum tolerated dose of HMPL-760 in subjects, if reached
Incidence of DLTs
Time Frame: Up to 28 days after first dose of study drug
Adverse event (AE) that meets protocol defined DLT criteria during dose escalation
Incidence of AEs/SAEs
Time Frame: From 1st dose to within 30 days of last dose
Any untoward medical occurrence associated with the use of study drug
RP2D
Time Frame: From 1st dose to within 30 days of last dose
To determine recommended phase 2 dose of HMPL-760 in subjects
Secondary Outcomes
- Objective Response Rate (ORR)(From 1st dose of study drug to the time of progressive disease, assessed up to 36 months)
- Duration of Response (DoR)(From first dose of study drug to the time of progressive disease, assessed up to 36 months)
- Clinical Benefit Rate (CBR)(From 1st dose of study drug to the time of progressive disease, assessed up to 36 months)
- Progression-free Survival (PFS)(From 1st dose of study drug to the time of progressive disease, assessed up to 36 months)
- Maximum Plasma Concentration [Cmax](From 1st dose to within 30 days of last dose)
- Chemokines(From 1st dose to within 30 days of last dose)
- Phospho-BTK(From 1st dose to within 30 days of last dose)