Clinical trial NCT05190068: HMPL-760 in Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: B-Cell Non-Hodgkin's Lymphoma
Keywords: B-Cell Non-Hodgkin's Lymphoma
Bruton's tyrosine kinase inhibitor
Lead sponsor: Hutchmed
Sponsor class: INDUSTRY
First posted: 2022-01-13
Enrollment: 89
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

Eligibility criteria: Inclusion Criteria:

1. Signed Informed Consent Form (ICF)
2. Age ≥18 years
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. In the expansion stage, ECOG performance status 0-2
4. 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.
5. 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.
6. Expected survival longer than 24 weeks

Exclusion Criteria:

Patients who met any of the following criteria are excluded from the study:

1. Lymphoma patients with central nervous system (CNS) or leptomeningeal invasion
2. Inadequate organ function of liver and kidney
3. 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)
4. Any anti-tumor therapy including chemotherapy and radiotherapy within 3 weeks prior to the first dose of study drug
5. 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.
6. 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
7. Prior use of any anti-tumor vaccine
8. Prior administration of radioimmunotherapy within 3 months prior to the first dose of study drug
9. Any uncontrolled active infection
10. History of drug-induced interstitial pneumonia

Primary outcomes:
measure: DLTs
timeFrame: Up to 28 days after first dose of study drug.
measure: Safety and Tolerability
timeFrame: Baseline up to the end of study
Secondary outcomes:
measure: Objective response rate (ORR)
timeFrame: Baseline up to 6 months after the last patient was enrolled
measure: Complete response rate (CR rate)
timeFrame: Baseline up to 6 months after the last patient was enrolled
measure: Progression-free survival (PFS)
timeFrame: Baseline up to 6 months after the last patient was enrolled
measure: Time to Response (TTR)
timeFrame: Baseline up to 6 months after the last patient was enrolled
measure: Clinical Benefit Rate (CBR)
timeFrame: Baseline up to 6 months after the last patient was enrolled
measure: Duration of Response (DoR)
timeFrame: Baseline up to 6 months after the last patient was enrolled
measure: Overall Survival (OS)
timeFrame: Baseline up to 6 months after the last patient was enrolled
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Chao-Yang Hospital, Capital Medical University
state: Beijing
city: Xiameng
country: China
facility: The First Affiliated Hospital of Xiamen University
state: Fujian
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
city: Nanning
country: China
facility: Guangxi Medical University cancer Hospital & Guangxi Cancer Institute
state: Guangxi Zhuang Autonomous Region
city: Chengde
country: China
facility: Affiliated Hospital of Chengde Medical University
state: Hebei
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Wuhan
country: China
facility: Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology
state: Hubei
city: Chenzhou
country: China
facility: Chenzhou First People's Hospital
state: Hunan
city: Suzhou
country: China
facility: First Affiliated Hospital of Soochow University
state: Jiangsu
city: Nanchang
country: China
facility: Jiangxi Cancer Hospital
state: Jiangxi
city: Changchun
country: China
facility: Jilin Cancer Hospital
state: Jilin
city: Dalian
country: China
facility: The Second Affiliated Hospital of Dalian Medical University
state: Liaoning
city: Shenyang
country: China
facility: The First Hospital of China Medical University
state: Liaoning
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
state: Longjiang Hei
city: Jinan
country: China
facility: Qilu Hospital of Shandong University
state: Shandong
city: Changzhi
country: China
facility: Heping Hospital Affiliated to Changzhi Medical College
state: Shanxi
city: Taiyuan
country: China
facility: Shanxi Bethune Hospital
state: Shanxi
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
state: Sichuan
city: Hangzhou
country: China
facility: Affiliated Hangzhou First People's Hospital ,Zhejiang University School of Medicine
state: Zhejiang
city: Chongqing
country: China
facility: Chongqing university cancer hospital
city: Shanghai
country: China
facility: Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Study officials:
affiliation: Shanghai Jiao Tong University School of Medicine
name: Weili Zhao, Ph.D
role: PRINCIPAL_INVESTIGATOR
References: