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FDA approves all-oral DEC-C plus venetoclax for patients with newly diagnosed AML ineligible for intensive chemotherapy

On May 13, 2026, the U.S. Food and Drug Administration (FDA) approved an all-oral regimen of decitabine–cedazuridine (DEC-C; ASTX727) plus venetoclax for the treatment of patients with newly diagnosed acute myeloid leukemia (AML) ineligible for intensive induction chemotherapy (ICT).1

This approval is based on data from the ASCERTAIN-V trial (NCT04657081), which enrolled patients with AML aged 75 years or older or with comorbidities precluding first-line intensive induction chemotherapy.2 Of the 101 evaluable patients (median age = 78) treated with DEC-C plus venetoclax, 41.6% (95% CI: 31.9–51.8) achieved a complete response (CR), as defined by the European LeukemiaNet (ELN) 2017 response criteria, meaning the primary endpoint of the study was met.1 The median time to CR was two months (range: 0.4–15.3 months), and the median duration of CR was not reached (range: 0.5 to 16.3 months).1 

Data from the Phase IIb portion of the study were also presented last year at the 30th Congress of the European Hematology Association (EHA) and the 2025 ASCO Annual Meeting. At a median follow-up of 11.2 months, 46.5% (95% CI: 36.5%–56.7%) of the 101 evaluable patients achieved a CR.3 Additionally, the CR/CR with incomplete hematologic recovery (CRi) rate was 63.4% (95% CI: 53.2%–72.7%).3 The median time to achieve CR was 2.4 months, and the median CR duration was not reached. In those who achieved CR, response persisted in 80.0% at 6 months and 75.3% at 12 months. A median overall survival (OS) of 15.5 months (95% CI: 7.6-not estimable) was reported.3

Regarding the safety of this combination regimen, Grade ≥3 treatment-emergent adverse events were reported in 98.0% of patients, with the most common adverse events being febrile neutropenia (49.5%), anemia (38.6%), and neutropenia (35.6%).3 The 30- and 60-day mortality rates in this cohort were 3.0% and 9.9%, respectively. To mitigate myelosuppression-related toxicity observed in Phase I of the trial, dose adjustments of DEC-C and/or venetoclax were permitted after Cycle 1 in the Phase IIb portion. These dose reductions were guided by achievement of disease remission on bone marrow examination. As a result, the proportion of patients remaining on full 28-day venetoclax dosing in Cycles 1/2 decreased across the Phases of the study; however, respective median OS increased.3 

At EHA 2025, we spoke with Gail Roboz, MD, Weill Cornell Medicine, New York City, NY, who presented this encouraging trial data from ASCERTAIN-V at the meeting. Dr Roboz stated, “So we are very much hoping that this can be a potential new standard of care for patients. …the goal would be to get patients to be able to spend more time at home. …that doesn’t mean that you can give patients pills and send them home and say, good luck – these patients need monitoring …but what we tried to show with these data, would be that patients who are doing well can, in fact, spend more time at home because they don’t have to come in for parenteral administration. And also in the post-remission setting, once you have blast clearance and demonstrate a response, the idea is that the dosing days of venetoclax go down.”

Based on data from ASCERTAIN-V, the all-oral combination of DEC-C and venetoclax had a safety profile and survival rates comparable to those of parenteral azacitidine plus venetoclax in a population of newly diagnosed AML patients ineligible for ICT. Additionally, early bone marrow examinations could be used to inform subsequent dose reductions of DEC-C and/or venetoclax in the post-remission setting, and these were associated with superior long-term outcomes and tolerability. The approval of this regimen provides an efficacious, all-oral treatment option for this patient population, addressing a significant unmet need.

References

  1. U.S. Food and Drug Administration. FDA approves oral combination of decitabine and cedazuridine tablets with venetoclax for newly diagnosed acute myeloid leukemia. Available here. (Last accessed 18/05/2026)
  2. ClinicalTrials.gov. Pharmacokinetics, Safety, and Efficacy of ASTX727 in Combination With Venetoclax in Acute Myeloid Leukemia (AML). Available here. (Last accessed 22/02/2026). 
  3. Roboz G, Zeidan A, Mannis G, et al. All-oral decitabine-cedazuridine (DEC-C) + venetoclax (VEN) in patients with newly diagnosed acute myeloid leukemia (AML) ineligible for induction chemotherapy: Phase 1/2 clinical trial results. Abstract S135. Presented at the 2025 Congress of the European Hematology Association; June 12–15, 2025; Milan, Italy.

Written by Natalie Markova

Reviewed by Anya Dragojlovic Kerkache