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

Phase 1 Open-label Dose Escalation and Expansion Study of ZEN003365 in Subjects With Relapsed or Refractory Lymphoproliferative Malignancies or Acute Myeloid Leukemia

The purpose of this study is to determine safety, tolerability, dose limiting toxicities (DLT) and maximum tolerated dose (MTD) of ZEN003365 in patients with relapsed/refractory lymphoproliferative malignancies (LPM) or relapsed/refractory acute myeloid leukemia (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