HMPL-760 in Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma

Study Overview
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Brief Summary
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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
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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).

Official Title
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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

Conditions
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B-Cell Non-Hodgkin's Lymphoma

Intervention / Treatment
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* Drug: HMPL-760


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed Informed Consent Form (ICF) Age ≥18 years Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. In the expansion stage, ECOG performance status 0-2 Relapsed/refractory patients with histologically confirmed lymphoma or cytologically confirmed CLL (flow cytometry) At least one bidimensionally measurable lesion by CT with the exception of CLL, i.e., nodal lesions > 1.5 cm in maximal diameter or extranodal lesions > 1.0 cm; Expected survival longer than 24 weeks Exclusion Criteria: 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 Receipt of small molecule targeted therapy with approved anti-tumor therapy within 7 days or approximately 5 half-lives (whichever is longer) prior to the first dose of study drug 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Relapsed/refractory B-NHL<br>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. | Drug: HMPL-760<br>* HMPL-760 was administered continuously as a single agent orally every day in sequential 28-day cycles.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DLTs | 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 | Up to 28 days after first dose of study drug. | 
| Safety and Tolerability | Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 | Baseline up to the end of study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) | Defined as the proportion of patients with CR/Partial response (PR)/CR with incomplete hematologic recovery (CRi)/ partial response with lymphocytosis (PR-L) | Baseline up to the last patient has completed 12 months after treatment | 
| Complete response rate (CR rate) | Defined as the proportion of patients with CR/CRi | Baseline up to the last patient has completed 12 months after treatment | 
| Progression-free survival (PFS) | Defined as the time from the first dose of HMPL-760 to occurrence of Progressive disease (PD) or death, whichever comes first | Baseline up to the last patient has completed 12 months after treatment | 
| Time to Response (TTR) | Defined as the time from the first dose of HMPL-760 to the first objective response | Baseline up to the last patient has completed 12 months after treatment | 
| Clinical Benefit Rate (CBR) | Defined as the proportion of patients with CR/CRi, PR/PR-L and Stable disease (SD) | Baseline up to the last patient has completed 12 months after treatment | 
| Duration of Response (DoR) | Defined as the time from the initial objective response to disease recurrence, progression or death | Baseline up to the last patient has completed 12 months after treatment | 
| Overall Survival (OS) | Defined as the time from the first dose to death due to any cause | Baseline up to the last patient has completed 60 months after treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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B-Cell Non-Hodgkin's Lymphoma, Bruton's tyrosine kinase inhibitor