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

Phase 3

Terminated

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

Interventions: Drug: Rituximab
Drug: Zandelisib
Drug: Bendamustine
Drug: CHOP

Brief Summary: 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: 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.

Recruitment & Eligibility

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:
1. FL Gr 1, Gr 2, or Gr 3a
2. 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

Arm && Interventions

Group	Intervention	Description
Rituximab plus chemotherapy	Rituximab	Rituximab and Bendamustine or Rituximab with (CHOP) for 6 cycles
Rituximab plus chemotherapy	Bendamustine	Rituximab and Bendamustine or Rituximab with (CHOP) for 6 cycles
Rituximab plus chemotherapy	CHOP	Rituximab and Bendamustine or Rituximab with (CHOP) for 6 cycles
Rituximab plus Zandelisib	Zandelisib	Rituximab plus Zandelisib for 6 cycles followed by Zandelisib for 20 cycles
Rituximab plus Zandelisib	Rituximab	Rituximab plus Zandelisib for 6 cycles followed by Zandelisib for 20 cycles

Primary Outcome Measures

Name	Time	Method
Progression Free Survival	1 year 7 months	PFS is defined as the time from randomization date until the date of disease progression, or death from any cause

Secondary Outcome Measures

Name	Time	Method
Overall Response Rate (ORR)	1 year 7 months	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.
Complete Response Rate (CRR)	1 year 7 months	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).
Overall Survival	1 year 7 months	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.
Number of Treatment Emergent AEs (Zandelisib When Combined With Rituximab)	1 year 7 months	Measured by the number of Treatment Emergent AEs
Number of SAEs (Zandelisib When Combined With Rituximab)	1 year 7 months	Measured by the number of SAEs
Number of Lab Abnormalities (Zandelisib When Combined With Rituximab)	1 year 7 months	Measured by the number of laboratory abnormalities

Locations (138): The Oncology Institute of Hope and Innovation
🇺🇸
Riverside, California, United States
Orange Coast Memorial Medical Center
🇺🇸
Fountain Valley, California, United States
Long Beach Memorial Medical Center
🇺🇸
Long Beach, California, United States
BRCR Medical Center Inc
🇺🇸
Hollywood, Florida, United States
Henry Ford Hospital
🇺🇸
Detroit, Michigan, United States
Revive Research Institute
🇺🇸
Sterling Heights, Michigan, United States
Mercy Clinic Cancer & Hematology - Chub O'Reilly Cancer Center
🇺🇸
Springfield, Missouri, United States
Inspira Medical Center Mullica Hill
🇺🇸
Mullica Hill, New Jersey, United States
MetroHealth Medical Center
🇺🇸
Cleveland, Ohio, United States
Alpha Research Institute, LLC
🇺🇸
Baytown, Texas, United States
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The Oncology Institute of Hope and Innovation
🇺🇸Riverside, California, United States