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