A Study of ME-401 in Subjects With CLL/SLL, FL, and B-cell Non Hodgkin’s Lymphoma

Inclusion Criteria MEI-401 Alone:

Diagnosis of relapsed/refractory CLL and/or relapsed/refractory SLL or FL
No prior therapy with PI3Kd inhibitors
No prior therapy with Bruton tyrosine kinase (BTK) inhibitors unless the subject was intolerant of BTK therapy or subject had disease progression
Subjects with CLL/SLL must have prior treatment with BTK inhibitor and must have had progression or recurrence while on treatment of within 12 mos from BTK treatment
Subject must have failed at least 1 prior systemic therapy
QT-interval corrected according to Fridericia's formula (QTcF) ≤ 450 milliseconds (ms)
Left ventricular ejection fraction > 50%
For subjects, except those with CLL, must have at least one bi-dimensionally measurable nodal lesion >1.5 cm, as defined by Lugano Classification
Willingness to participate in collection of pharmacokinetic samples
A negative serum pregnancy test within 14 days of study Day 0, for females of childbearing potential

Inclusion Criteria ME-401 in Combination with Rituximab

Diagnosis of relapsed/refractory CLL SLL or FL, MZL, DLBCL and high-grade B-cell lymphoma. Subjects must meet the following criteria for relapsed or refractory disease:
No prior therapy with PI3Kδ inhibitors
No prior therapy with Bruton tyrosine kinase (BTK) inhibitors unless the subject was intolerant of BTK therapy or subject had disease progression
Subjects with CLL, SLL, FL, and MZL must have a failure of at least 1 prior systemic therapy and be considered by the investigator a candidate for therapy with a rituximab-based regimen; subjects with DLBCL and high-grade B-cell lymphoma must have a failure of at least 2 prior therapies.
QT-interval corrected according to Fridericia's formula (QTcF) ≤450 milliseconds (ms)
Left ventricular ejection fraction > 50%
For subjects, except those with CLL, must have at least one bi-dimensionally measurable nodal lesion >1.5 cm, as defined by Lugano Classification
Willingness to participate in collection of pharmacokinetic samples
A negative serum pregnancy test within 14 days of study Day 0 for females of childbearing potential

Inclusion Criteria ME-401 in Combination with Zanubrutinib

Diagnosis of relapsed/refractory CLL or histologically-confirmed relapsed/refractory SLL or FL, MZL, MCL, DLBCL NOS (germinal center B-cell type or activated B-cell type)
No prior therapy with PI3Kδ inhibitors
No prior therapy with BTK inhibitors
Subjects with CLL, SLL, FL, MCL, and MZL must have a failure of at least 1 prior systemic therapy, require treatment in the opinion of the investigator, and be considered by the investigator a candidate for therapy subjects with DLBCL and high-grade B-cell lymphoma must have a failure of at least 2 prior therapies
For subjects with SLL, FL, MZL, MCL, DLBCL: At least one bi dimensionally measurable nodal lesion > 1.5 cm in its longest diameter by CT scan or MRI
QT-interval corrected according to Fridericia's formula (QTcF) ≤ 450 milliseconds (msec)
Left ventricular ejection fraction > 50% as measured by echocardiogram or multigated acquisition (MUGA) scan
Willingness to participate in collection of pharmacokinetic samples
For females of childbearing potential, a negative serum pregnancy test within 14 days of study Day 0

Exclusion Criteria:

Known histological transformation from CLL to an aggressive lymphoma
Uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia
Subjects who have tested positive for hepatitis B surface antigen and/or hepatitis B core antibody
Positive for hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) antibody
Ongoing drug-induced pneumonitis
History of clinically significant cardiovascular abnormalities
History of severe bleeding disorders (ME-401 plus zanubrutinib arm only)
Known central nervous system (CNS) hemorrhage or stroke within 6 months prior to start of study drugs (ME-401 plus zanubrutinib arm only)