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

A Three-Arm Study of ME-401 in Subjects with Relapsed/Refractory CLL/SLL or FL, of ME-401 in Combination with Rituximab in Subjects with Relapsed/Refractory CLL/SLL or B-cell NHL, and of ME-401 in Combination with Zanubrutinib in Subjects with Relapsed/Refractory CLL/SLL or B-cell NHL

This is a three-arm study of ME-401 alone, of ME-401 in combination with rituximab, and of ME-401 in combination with zanubrutinib in subjects with relapsed/refractory CLL/SLL or B cell NHL. The 3 arms of the study will be conducted in parallel, with subject allocation to ME-401 alone, ME-401 plus rituximab, or ME-401 plus zanubrutinib based on disease type and availability of an open enrollment slot.

Eligibility Criteria:
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)