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