Zandelisib (ME-401) in Subjects With Follicular Lymphoma or Marginal Zone Lymphoma After Failure of Two or More Prior Therapies (TIDAL)

Study Overview
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Brief Summary
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This is the study of the PI3Kδ inhibitor Zandelisib (ME-401) in subjects with relapsed/refractory follicular lymphoma or marginal zone lymphoma after failure of at least 2 prior lines of systemic therapy

Detailed Description
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This is a global, multicenter open-label, single-arm, Phase 2 study of the PI3Kδ inhibitor Zandelisib (ME-401) in subjects with relapsed/refractory follicular lymphoma or marginal zone lymphoma after failure of at least 2 prior lines of systemic therapy which must have included an anti-CD20 antibody and chemotherapy with an alkylating agent or a purine analogue. Approximately 180 subjects will be enrolled and treated with Zandelisib (ME-401) on the intermittent schedule.

Official Title
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A Multicenter, Open Label Single-Arm, Phase 2 Study of Zandelisib (ME-401) in Subjects With Follicular Lymphoma and Marginal Zone Lymphoma After Failure of Two or More Prior Systemic Therapies (The TIDAL Study)

Conditions
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Follicular Lymphoma (FL), Non Hodgkin Lymphoma, Marginal Zone Lymphoma

Intervention / Treatment
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* Drug: Zandelisib (ME-401)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed diagnosis as defined in the World Health Organization (WHO) classification scheme Follicular Lymphoma (FL) limited to Grade 1,2 or 3a or Marginal Zone Lymphoma (MZL) including nodal, extranodal and splenic MZL Subjects that have had progression of disease or had no response to therapy after at least 2 prior systemic therapies for FL or MZL Age ≥ 18 At least one bi-dimensionally measurable nodal lesion > 1.5 cm in its longest diameter by computed tomography (CT) scan as defined by the Lugano Classification Adequate hematologic, renal and hepatic parameters at screening unless abnormal values are due to FL per Investigator assessment QT-interval corrected according to Fridericia's formula (QTcF) ≤ 450 milliseconds (msec); Left ventricular ejection fraction (LVEF) ≥ 45% Exclusion Criteria: Histologically confirmed FL Grade 3b transformation from FL to an aggressive lymphoma Known lymphomatous involvement of the central nervous system Uncontrolled clinically significant illness Ongoing or history of drug-induced pneumonitis History of clinically significant cardiovascular abnormalities History of clinically significant GI conditions Known history of, or active HIV infection

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
Interventional Model Description: Treatment with Zandelisib (ME-401) (60 mg) given orally once a day on an intermittent schedule
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Zandelisib (ME-401) open label<br>Subjects with relapsed/refractory FL or MZL will be administered 60 mg of ME-401 orally, once a day on an intermittent schedule (IS). | Drug: Zandelisib (ME-401)<br>* Zandelisib (ME-401) 60 mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) of ME-401 in relapsed or refractory FL or MZL based on the Independent Review Committee assessment | ORR is measured as the proportion of subjects achieving the best response rating of CR or PR prior to first PD | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of response (DOR) | Duration of Response will be measured as the time from documentation from CR or PR to time of disease progression | 2 years | 
| Complete response (CR) rate | Complete response rate will be measured by the number of subjects that achieve CR | 2 years | 
| Progression-free survival (PFS) | Progression-free survival will be measurement of time from initiation of treatment (Day 1) until disease progression or death | 2 years | 
| Overall Survival | Overall survival will be measured as the time from initiation of treatment (Day 1) until death | 2 years | 
| Overall incidence of treatment emergent adverse events (TEAEs) | The incidence of TEAEs is measured by the proportion of subjects with at least one TEAE. | 2 years | 
| PK of ME-401 | The PK of ME-401 will be determined by the peak plasma concentration (Cmax) | 6 months |