Sponsor decision

A Phase 1/2 dose escalation study of BCL-2 Inhibitor ZN-d5 and the Wee1 Inhibitor ZN-c3 in Subjects with Acute Myeloid Leukemia (AML).

This is an open-label multicenter Phase 1/2 dose escalation study, evaluating the safety, tolerability, clinical activity, pharmacokinetics and pharmacodynamics of the novel BCL-2 inhibitor ZN-d5 and Wee1 inhibitor ZN-c3 in subjects with AML.

Inclusion Criteria:

• Adults with AML (including secondary or therapy-related), relapsed from or refractory to one or more prior lines of therapy, which may include venetoclax except in Expansion Cohort A
• ECOG performance status score ≤2.
• Projected life expectancy of at least 12 weeks.
• Estimated glomerular filtration rate ≥60 mL/min
• Women of childbearing potential must not be pregnant and must use effective birth control during the study and for 6 months after the last dose of study drugs.
• Men must agree to use a condom when having intercourse during the study and for 3 months after the last dose of study drugs.

Exclusion Criteria:

• Known active CNS involvement
• Diagnosis of acute promyelocytic leukemia.
• Peripheral blast count of >25 × 109/L (cytoreduction permitted).
• Adequate washout from prior therapy including hematopoietic stem cell transplant and recovery from prior treatment-related toxicities to Grade 2 or lower
• Significant cardiovascular disease
• Corrected QT interval (QTc) of >480 msec
• Active hepatitis B or hepatitis C infection
• Concurrent treatment with strong CYP3A inhibitors or strong or moderate CYP3A inducers