ASCERTAIN-V trial: All-oral DEC-C + venetoclax regimen in newly diagnosed AML

The combination of venetoclax (Ven) + azacitidine (Aza) + decitabine (Dec), or low-dose cytarabine (LDAC) is approved by the U.S. Food and Drug Administration for the treatment of patients with newly diagnosed acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy. Parenteral Dec or Aza regimens are associated with a significant treatment burden on patients; oral Dec + cedazuridine (DEC-C) has an equivalent pharmacokinetic area under the curve to intravenous Dec. During the European Hematology Association (EHA) 2025 Congress, June 12–15, 2025, Milan, IT, Gail Roboz presented key findings from the phase I/II ASCERTAIN-V trial (NCT04657081) assessing the safety and efficacy of the all-oral DEC-C + Ven regimen in older patients aged ≥75 years with newly diagnosed AML, who were ineligible for first-line intensive chemotherapy.

All patients (N = 189) received oral DEC-C on Days 1–5 + Ven 400 mg daily in 28-day cycles after Cycle 1. During Cycle 1, Ven was ramped up to 100 mg on Day 1, 200 mg on Day 2, and 400 mg on Day ≥3. The primary endpoints were the effect of DEC-C on Ven pharmacokinetic exposures for phase I and the complete remission rate for phase IIa/b. Secondary endpoints included response rates, duration of response, overall survival, and safety. 

Key learnings

The primary objective of phase I was met with no DDI effect observed between DEC-C and Ven (AUC_0–24 Geo LSM ratio, 102.0%).

The CR rates were 40.0%, 37.9%, and 46.5% in phase I (n = 30), phase IIa (n = 58), and phase IIb (n = 101), while the CRc (CR + CRi + CRh) rates were 63.3%, 65.5%, and 63.4%, respectively. At 9 months, CR persisted in 75%, 76.2%, and 80.0% of patients in phases I, IIa, and IIb, respectively.

The median OS was 6.8 months in phase I, 14.5 months in phase IIa, and 15.5 months in phase IIb. Among patients achieving CRc in phase IIb (n = 49), 55.1% were MRD negative.

The BM assessment at C1, D22 showed an increase in rates from 3.3% in phase I to 15.5% in phase IIa to 31.7% in phase IIb, while the mean number of dosing days decreased from phase I to IIb for both DEC-C and Ven.

Grade 3–4 TRAEs were observed in 63.3%, 63.8%, and 72.3% of patients treated with DEC-C + Ven in phases I, IIa, and IIb, respectively. Myelosuppression was the most common Grade 3–4 TRAE across all phases.

All oral DEC-C + Ven regimen has the potential to change clinical practice for older patients with AML who have high unmet needs.