Clinical Study of HMPL-689 for Relapsed/Refractory Marginal Zone Lymphoma and Follicular Lymphoma

Study Overview
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Brief Summary
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A Multi-center, Single-arm, Open-label Clinical Study to Evaluate the Efficacy and Safety of HMPL-689 in Patients with Relapsed/Refractory Marginal Zone Lymphoma (MZL) and Follicular Lymphoma (FL)

Detailed Description
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This is a multi-center, single-arm, open-label clinical study to evaluate the oral therapy with HMPL-689 in patients with relapsed / refractory MZL and FL. Relapse / refractory is defined as such a situation when a patient has not achieved response (CR or PR) after the latest line of systemic treatment, or has disease progress (PD) or relapse after achieving response. Two (2) cohorts of patients will be enrolled in this study: Cohort 1: approximately 81 patients with histologically confirmed MZL Cohort 2: approximately 104 patients with histologically confirmed FL (pathological grade 1-3a) All patients are to receive monotherapy of HMPL-689 30 mg once a day (QD) continuously in 28-day treatment cycles until PD / recurrence, patient death, intolerable toxicity, initiation of other antitumor therapy, the patient unable to further benefit from the study treatment as judged by the investigators, the patient or his/her legal representative's request to withdraw from the clinical study treatment, the patient lost to follow-up or end of the study, whichever comes first.

Official Title
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A Multi-center, Single-arm, Open-label Clinical Study to Evaluate the Efficacy and Safety of HMPL-689 in Patients With Relapsed/Refractory Marginal Zone Lymphoma and Follicular Lymphoma

Conditions
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Marginal Zone Lymphoma, Follicular Lymphoma

Intervention / Treatment
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* Drug: HMPL-689


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years; Patients with relapsed/refractory marginal zone lymphoma or follicular lymphoma Eastern Cooperative Oncology Group (ECOG) Performance Status score 0-2; At least one measurable lesion by computerised tomography (CT) / magnetic resonance imaging (MRI) (the longest diameter of nodal lesion > 1.5 cm or extranodal lesion > 1 cm); Expected survival of more than 12 weeks; Exclusion Criteria: Having lymphoma with central nervous system (CNS) or cerebral pia mater invasion Known histologic transformation to aggressive lymphomas such as diffuse large B-cell lymphoma (DLBCL); Prior use of any phosphatidylinositol 3-kinase (PI3K) inhibitor or Bruton's tyrosine kinase (BTK) inhibitor Inadequate organ function of liver and kidney Currently known active infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) Having received systemic antitumor therapy or radiotherapy within 4 weeks prior to the first dose of the investigational product Toxicity of previous antitumor therapy not recovered to CTCAE grade ≤ 1, except alopecia, prior to the first dose of the investigational product Complicated with uncontrolled systemic infection requiring intravenous antibiotic treatment Pregnant (positive serum pregnancy test) or lactating women Any other disease, metabolic abnormality, physical examination abnormality or clinically significant laboratory test abnormality, one disease or state providing a reason to suspect that the subject is not suitable for HMPL-689 at the investigator's discretion, or one condition that will affect interpretation of the study results or bring the subject at high risk.

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 MZL and FL<br>Relapsed/Refractory Marginal Zone Lymphoma and Follicular Lymphoma | Drug: HMPL-689<br>* All patients are to receive monotherapy of HMPL-689 30 mg QD continuously in 28-day treatment cycles.<br>* Other names: Phosphatidylinositol 3-kinase-δ inhibitor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate (ORR) | Defined as the proportion of patients with CR or PR | Baseline up to the last patient has completed 12 months after treatment. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response (CR) rate | Defined as the proportion of patients with CR. | 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-689 to occurrence of 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-689 to the first objective response. | 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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Marginal Zone Lymphoma, Follicular Lymphoma, Phosphatidylinositol 3-kinase inhibitor