Phase 3 Study of Zandelisib (ME-401) in Combination With Rituximab in Patients With iNHL - (COASTAL)

Study Overview
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Brief Summary
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This is a Phase 3 study of the PI3Kδ inhibitor Zandelisib (ME-401) in combination with rituximab, in comparison to standard immunochemotherapy (Rituximab-Bendamustine or Rituximab-CHOP) in subjects with relapsed or refractory FL and MZL.

Detailed Description
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This is an open label, randomized, two-arm Phase 3 study in subjects with relapsed or refractory FL and MZL to evaluate efficacy and safety of zandelisib in combination with rituximab in comparison to standard immunochemotherapy (Rituximab-Bendamustine or Rituximab-CHOP). Subjects must have relapsed after at least one previous line of systemic immunochemotherapy. Previous treatments must have included an anti-CD20 monoclonal antibody (mAb) with chemotherapy such as Bendamustine (B), CHOP, CVP, FND, or similar regimens, or an anti-CD20 mAb with Lenalidomide (L). Approximately 534 randomized subjects will be enrolled in this study.

Official Title
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A Phase 3, Randomized, Open-Label, Controlled, Multicenter Study of Zandelisib (ME- 401) in Combination With Rituximab Versus Standard Immunochemotherapy in Patients With Relapsed Indolent Non Hodgkin's Lymphoma (iNHL) - The COASTAL Study

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

Intervention / Treatment
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* Drug: Zandelisib
* Drug: Rituximab
* Drug: Bendamustine
* Drug: CHOP


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects ≥18 years of age, ≥19 years in Korea, or ≥20 years for subjects in Japan and Taiwan Histologically confirmed diagnosis of CD20 positive iNHL with histological subtype limited to: FL Gr 1, Gr 2, or Gr 3a MZL (splenic, nodal, or extra-nodal) Subjects with relapsed or refractory disease who received ≥1 prior lines of therapy Subjects must have at least one bi-dimensionally measurable lesion >1.5 cm Adequate hematologic parameters at screening unless abnormal values are due to disease Adequate renal and hepatic function Adequate cardiac function based on ECG and LVEF assessments Exclusion Criteria: Histologically confirmed diagnosis of FL Gr 3b or transformed disease Prior therapy with PI3K inhibitors Ongoing or history of drug-induced pneumonitis Known lymphomatous involvement of the central nervous system Tested positive for or active viral infection with hepatitis B or C virus Tested positive or active infection with human immunodeficiency virus Tested positive, or active infection with human T-cell leukemia virus type 1 Any uncontrolled clinically significant illness History of clinically significant cardiovascular abnormalities such as congestive heart failure History of clinically significant gastrointestinal (GI) conditions Females who are pregnant

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Arm 1: Rituximab plus Zandelisib Arm 2: Rituximab plus chemotherapy (CHOP or Bendamustine)
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rituximab plus Zandelisib<br>Rituximab plus Zandelisib for 6 cycles followed by Zandelisib for 20 cycles | Drug: Zandelisib<br>* Zandelisib 60 mg capsules taken daily for two cycles followed by intermittent schedule starting at Cycle 3<br>* Other names: ME-401;Drug: Rituximab<br>* Rituximab IV 375 mg/m2 for 6 cycles<br>* Other names: MabThera;|
| Experimental: Rituximab plus chemotherapy<br>Rituximab and Bendamustine or Rituximab with (CHOP) for 6 cycles | Drug: Rituximab<br>* Rituximab IV 375 mg/m2 for 6 cycles<br>* Other names: MabThera;Drug: Bendamustine<br>* Bendamustine IV 90 mg/m2 on Days 1 and 2 for 6 cycles<br>* Other names: Bendeka, Treanda, Belrapzo;Drug: CHOP<br>* Cyclophosphamide, Vindcristine IV, and Prednisone daily orally<br>* Other names: cyclophosphamide 750 mg/m2, hydroxydoxorubicin IV 50 mg/m2, vincristine IV 1.4 mg/m2 and prednisone 100 mg daily;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival | PFS is defined as the time from randomization date until the date of disease progression, or death from any cause | 1 year 7 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) | ORR is defined as the proportion of subjects who have a best overall response of CR or PR according to the Lugano Classification over the entire duration of the study, including the efficacy follow-up period. | 1 year 7 months | 
| Complete Response Rate (CRR) | CRR is defined as the proportion of subjects who have a best overall response of CR during the study (i.e., up to time of analysis of PFS). | 1 year 7 months | 
| Overall Survival | OS is defined as the time (in days) from randomization until death from any cause. For subjects alive at the time of analysis, they will be censored at the last documented alive date. | 1 year 7 months | 
| Number of Treatment Emergent AEs (Zandelisib When Combined With Rituximab) | Measured by the number of Treatment Emergent AEs | 1 year 7 months | 
| Number of SAEs (Zandelisib When Combined With Rituximab) | Measured by the number of SAEs | 1 year 7 months | 
| Number of Lab Abnormalities (Zandelisib When Combined With Rituximab) | Measured by the number of laboratory abnormalities | 1 year 7 months |