A Study of Voruciclib Alone or in Combination With Venetoclax in Subjects With B-Cell Malignancies or AML

Inclusion Criteria

• Age ≥18 years
• Histologically-confirmed diagnosis of Follicular lymphoma (FL), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), small lymphocytic lymphoma (SLL), chronic lymphocytic leukemia(CLL), diffuse large B-cell lymphoma (DLBCL), or AML a. Subjects must have disease that has relapsed or is refractory to 2 or more prior regimens and in need of treatment due to progressive disease
• Presence of measurable disease defined per the 2008 International workshop on CLL guidelines, or by 2014 Lugano criteria for non-Hodgkin lymphoma (does not apply for AML subjects)
• Adequate hematologic parameters unless clearly due to the disease under study
• Adequate renal and hepatic function, per laboratory reference range at screening

Exclusion Criteria

• History of pneumonitis of any cause
• For CLL subjects: only known histological transformation to an aggressive lymphoma
• For AML subjects:
• Acute promyelocytic leukemia
• Peripheral blast count > 25 × 10 9/L
• Known central nervous system involvement
• Significant cardiovascular disease
• Significant screening ECG abnormalities
• Subjects who require warfarin, anti-cancer therapeutics or investigational agents
• Evidence of an ongoing systemic bacterial, fungal, or viral infection (including upper respiratory tract infections) at the time of start of voruciclib therapy
• Prior solid organ transplantation
• Receipt of an allogeneic transplant within 6 months or an autologous transplant within the preceding 3 months; evidence of ongoing graft-versus-host disease (GVHD)
• Prior therapy with a cyclin-dependent kinase (CDK9) inhibitor
• Symptomatic/uncontrolled HIV infection/AIDS, or currently taking contraindicated medications for HIV control
• Ongoing immunosuppressive treatment including calcineurin inhibitors at the time of the start of study treatment, including systemic or enteric corticosteroids except as follows:
• Prior to the start of study treatment, subjects may be using systemic corticosteroids (≤20 mg/day of prednisone or equivalent), topical, or inhaled corticosteroids
• During study therapy, subjects may use systemic, topical, or enteric corticosteroids, if needed