NCT05176691撤回1 期
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)
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 发起方
- Hutchmed
- 试验地点
- 35
- 主要终点
- MTD
研究概览
简要总结
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
详细描述
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Treatment
Experimental
All patients to receive HMPL-760 daily.
干预措施: HMPL-760 (Drug)
结局指标
主要结局
MTD
时间窗: 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
时间窗: 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
时间窗: From 1st dose to within 30 days of last dose
Any untoward medical occurrence associated with the use of study drug
RP2D
时间窗: From 1st dose to within 30 days of last dose
To determine recommended phase 2 dose of HMPL-760 in subjects
次要结局
- 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)
研究者
研究点 (35)
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