Phase 1 Study Evaluating ZEN003365 in Relapsed/Refractory Lymphoproliferative Malignancies or Relapsed/Refractory AML

Inclusion Criteria:

Dose Escalation and Expansion Stages:

ECOG performance status ≤ 1 for LPM patients, ≤ 2 for AML patients
Age 18 years or older
Adverse events (AEs), except for alopecia, from any previous treatments must have recovered to eligibility levels from prior toxicity
Adequate renal, hepatic and coagulation function, as specified per protocol
Written informed consent granted prior to any study-specific screening procedures

LPM Patients:

Histologically confirmed lymphoproliferative malignancy
Have received prior protocol-specified disease-dependent prior treatments
Have measurable disease
Platelets ≥ 75,000/µL (≥50,000/µL if bone marrow involvement), absolute neutrophil count (ANC) ≥ 1,000/ µL, and hemoglobin (Hgb) ≥ 8 g/dL
Patients must have been off previous anticancer therapy for at least 3 weeks or 5 half-lives, whichever is longer, and the subject must have recovered to eligibility levels from prior toxicity

AML:

Refractory or relapsed AML patients, without curative intent, e.g., not a stem cell transplant candidate
Any prior chemotherapy must have been completed ≥ 2 weeks, any therapy with biologics must have been completed ≥ 4 weeks prior to day 1 of study treatment, and the participant must have recovered to eligibility levels from prior toxicity
Blast count ≤ 10,000/µL prior to initiation of therapy

Exclusion Criteria

Dose Escalation and Expansion Stages:

Prior exposure to a BET inhibitor
Prior allogeneic hematopoietic cell transplant
Chronic graft versus host disease
Known, active fungal, bacterial, and/or viral infection
Uncontrolled autoimmune hemolytic anemia or thrombocytopenia
Current subdural hematoma
CNS or leptomeningeal metastases
Requirement for medications or agents known to be sensitive CYP3A4 substrate drugs, CYP3A4 substrate drugs with a narrow therapeutic range or to be strong inhibitors/inducers of CYP3A4
Requirement for immunosuppressive agents
Evidence of significant cardiovascular disease or significant screening ECG abnormalities
Any medical conditions that, in the Investigator's opinion, would impose excessive risk to the patient.

AML patients:

Acute promyelocytic leukemia (APL)
Chronic myeloid leukemia (CML) in blast crisis