Studio internazionale volto a esaminare la sicurezza, la tollerabilità e l’efficacia di un farmaco sperimentale denominato ME-401 come potenziale trattamento per i pazienti affetti da leucemia linfatica cronica (CLL), linfoma linfocitico a piccole cellule (SLL) o linfoma follicolare (FL) recidivante/refrattario.

Drug: ME-401;Drug: Rituximab;Drug: Zanubrutinib

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 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, 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 PI3Kd 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)