Phase I/II ASCERTAIN-V trial: Decitabine/cedazuridine + venetoclax in ND AML

Results from the open-label, multicenter, non-randomized phase I/II ASCERTAIN-V trial, (NCT04657081) evaluating an all-oral decitabine/cedazuridine combination + venetoclax in 189 patients with newly diagnosed (ND) acute myeloid leukemia (AML) who were ineligible for intensive chemotherapy (IC), were published in the New England Journal of Medicine by Roboz et al. The phase I (n = 30) and IIa (n = 58) pharmacokinetic (PK) endpoints included the effect of decitabine/cedazuridine on venetoclax and potential drug–drug interactions (DDIs), assessed by the area under the curve during 0–24 hours (AUC_0–24) and maximum observed concentration (C_max) of venetoclax with or without decitabine/cedazuridine. The complete remission (CR) rate was the primary efficacy endpoint for both phase IIa and phase IIb (n = 101).

Key data: There were no DDIs between decitabine/cedazuridine and venetoclax across all phases. In phase IIa and IIb, a CR was achieved in 38% (95% confidence interval [CI], 26–52) and 47% (95% CI, 36–57) of patients, respectively, with a CR/CR with incomplete hematologic recovery (CRi) in 66% and 63% of patients, respectively. Median overall survival (OS) was 6.8, 14.5, and 15.5 months in phase I, IIa, and IIb, respectively. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 63%, 64%, and 72% of patients in phase I, IIa, and IIb, respectively, and treatment-related serious adverse events (SAEs) occurred in 23%, 28%, and 36% of patients, respectively. Across all phases, the most common TRAEs (all Grade 3–4) were anemia (26%), neutropenia (21%), febrile neutropenia (21%), and thrombocytopenia (14%).

Key learning: All-oral decitabine/cedazuridine + venetoclax demonstrated clinically meaningful efficacy in patients with ND AML ineligible for IC, with no DDIs or new safety signals.