HMPL-760 in Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma
- Registration Number
- NCT05190068
- Lead Sponsor
- Hutchmed
- Brief Summary
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
- Detailed Description
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).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 89
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Signed Informed Consent Form (ICF)
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Age β₯18 years
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Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. In the expansion stage, ECOG performance status 0-2
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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.
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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.
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Expected survival longer than 24 weeks
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Relapsed/refractory B-NHL HMPL-760 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.
- Primary Outcome Measures
Name Time Method DLTs 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 Baseline up to the end of study Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
- Secondary Outcome Measures
Name Time Method Complete response rate (CR rate) Baseline up to 6 months after the last patient was enrolled Defined as the proportion of patients with CR/CRi
Time to Response (TTR) Baseline up to 6 months after the last patient was enrolled Defined as the time from the first dose of HMPL-760 to the first objective response
Progression-free survival (PFS) Baseline up to 6 months after the last patient was enrolled Defined as the time from the first dose of HMPL-760 to occurrence of Progressive disease (PD) or death, whichever comes first
Objective response rate (ORR) Baseline up to 6 months after the last patient was enrolled Defined as the proportion of patients with CR/Partial response (PR)/CR with incomplete hematologic recovery (CRi)/ partial response with lymphocytosis (PR-L)
Duration of Response (DoR) Baseline up to 6 months after the last patient was enrolled Defined as the time from the initial objective response to disease recurrence, progression or death
Overall Survival (OS) Baseline up to 6 months after the last patient was enrolled Defined as the time from the first dose to death due to any cause
Clinical Benefit Rate (CBR) Baseline up to 6 months after the last patient was enrolled Defined as the proportion of patients with CR/CRi, PR/PR-L and Stable disease (SD)
Trial Locations
- Locations (22)
Beijing Chao-Yang Hospital, Capital Medical University
π¨π³Beijing, Beijing, China
The First Affiliated Hospital of Xiamen University
π¨π³Xiameng, Fujian, China
Sun Yat-sen University Cancer Center
π¨π³Guangzhou, Guangdong, China
Guangxi Medical University cancer Hospital & Guangxi Cancer Institute
π¨π³Nanning, Guangxi Zhuang Autonomous Region, China
Affiliated Hospital of Chengde Medical University
π¨π³Chengde, Hebei, China
The First Affiliated Hospital of Zhengzhou University
π¨π³Zhengzhou, Henan, China
Jilin Cancer Hospital
π¨π³Changchun, Jilin, China
Chenzhou First People's Hospital
π¨π³Chenzhou, Hunan, China
Jiangxi Cancer Hospital
π¨π³Nanchang, Jiangxi, China
The Second Affiliated Hospital of Dalian Medical University
π¨π³Dalian, Liaoning, China
The First Hospital of China Medical University
π¨π³Shenyang, Liaoning, China
Harbin Medical University Cancer Hospital
π¨π³Harbin, Longjiang Hei, China
Shanxi Bethune Hospital
π¨π³Taiyuan, Shanxi, China
Qilu Hospital of Shandong University
π¨π³Jinan, Shandong, China
Heping Hospital Affiliated to Changzhi Medical College
π¨π³Changzhi, Shanxi, China
West China Hospital of Sichuan University
π¨π³Chengdu, Sichuan, China
Affiliated Hangzhou First People's Hospital ,Zhejiang University School of Medicine
π¨π³Hangzhou, Zhejiang, China
Henan Cancer Hospital
π¨π³Zhengzhou, Henan, China
Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology
π¨π³Wuhan, Hubei, China
First Affiliated Hospital of Soochow University
π¨π³Suzhou, Jiangsu, China
Chongqing university cancer hospital
π¨π³Chongqing, China
Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
π¨π³Shanghai, China