A Multicenter, Open-label, Phase I Study to Evaluate the Safety, Pharmacokinetics, and Preliminary Efficacy of HMPL-760 in Patients With Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Hutchmed
- 入组人数
- 89
- 试验地点
- 22
- 主要终点
- DLTs
研究概览
简要总结
A Multicenter, Open-label, Phase I Study to Evaluate the Safety, Pharmacokinetics, and Preliminary Efficacy of HMPL-760 in Patients with Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma
详细描述
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of HMPL-760 administered orally in subjects with relapsed/refractory B-cell non-Hodgkin lymphoma (B-NHL). Patients with relapsed/refractory B-NHL, including chronic lymphocytic leukemia/small cell lymphoma (CLL/SLL), diffuse large B-cell lymphoma (DLBCL), follicular cell lymphoma (FL), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), and lymphoplasmacytic/macroglobulinemia (LPL/WM).
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
- •Signed Informed Consent Form (ICF)
- •Age ≥18 years
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •In the expansion stage, ECOG performance status 0-2
- •Relapsed/refractory patients with histologically confirmed lymphoma
- •CLL confirmed by cytology (flow cytometry)
- •LPL/WM diagnosed by relevant tests including serum, bone marrow, and pathological examinations.
- •Except for CLL and WM, at least one bidimensionally measurable lesion is required by CT scan, which means the largest diameter of lymph node lesions >1.5 cm or extranodal lesions >1.0 cm; For lesions that cannot be well displayed by CT due to anatomical location (such as limb or soft tissue lesions), MRI measurement can be used.
- •Expected survival longer than 24 weeks
排除标准
- •Patients who met any of the following criteria are excluded from the study:
- •Lymphoma patients with central nervous system (CNS) or leptomeningeal invasion
- •Inadequate organ function of liver and kidney
- •Carcinoma in situ of the breast History of liver disease, including cirrhosis, alcoholism, or currently known active infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV)
- •Any anti-tumor therapy including chemotherapy and radiotherapy within 3 weeks prior to the first dose of study drug
- •Within 7 days or approximately 5 half-lives (whichever is longer) prior to the first dose of the investigational drug, received any corticosteroids or approved small molecule targeted anti-cancer therapies.
- •Any monoclonal antibody used for anti-tumor therapy within 4 weeks or 2 half-lives prior to the first dose of study drug, whichever is longer
- •Prior use of any anti-tumor vaccine
- •Prior administration of radioimmunotherapy within 3 months prior to the first dose of study drug
- •Any uncontrolled active infection
- •History of drug-induced interstitial pneumonia
研究组 & 干预措施
Relapsed/refractory B-NHL
The starting dose of HMPL-760 is initially set as 50 mg, and then the doses of 100 mg, 200 mg, 300 mg, and 400 mg are escalated successively (this dose gradient is assumed).
HMPL-760 was administered continuously as a single agent orally every day in sequential 28-day cycles.
干预措施: HMPL-760 (Drug)
结局指标
主要结局
DLTs
时间窗: Up to 28 days after first dose of study drug.
Number of subjects with Dose Limiting Toxicities (DLTs) with relapsed/refractory B-cell non-Hodgkin's lymphoma relapsed/refractory B-cell non-Hodgkin's lymphoma
Safety and Tolerability
时间窗: Baseline up to the end of study
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
次要结局
- Clinical Benefit Rate (CBR)(Baseline up to 6 months after the last patient was enrolled)
- Complete response rate (CR rate)(Baseline up to 6 months after the last patient was enrolled)
- Time to Response (TTR)(Baseline up to 6 months after the last patient was enrolled)
- Progression-free survival (PFS)(Baseline up to 6 months after the last patient was enrolled)
- Objective response rate (ORR)(Baseline up to 6 months after the last patient was enrolled)
- Duration of Response (DoR)(Baseline up to 6 months after the last patient was enrolled)
- Overall Survival (OS)(Baseline up to 6 months after the last patient was enrolled)