Idasanutlin plus Cytarabine. Participants are treated with 300 mg idasanutlin administered orally twice daily and intravenous cytarabine once daily for 5 days followed by 23 days of rest (Cycle 1). Responding patients may continue to receive a maximum of further two cycles of consolidation (Cycle 2 and Cycle 3).

Acute myeloid leukemia (AML) cell cultures were treated with idasanutlin alone (0.6–2000nM) or in combination with venetoclax. Combination treatment results in synergistic anti-tumor activity compared with the respective single-agent treatments in vitro, in p53 wild-type AML cell lines, and leads to strongly superior efficacy in vivo, in subcutaneous and orthotopic AML models. The inhibitory effects of idasanutlin were cell-cycle dependent, with cells arresting in G1 in consecutive cycles and the induction of apoptosis only evident after cells had gone through at least two cell cycles.