Decitabine/Cedazuridine Plus Venetoclax sNDA Under FDA Review for Newly Diagnosed AML

The FDA has accepted for review a supplemental new drug application (sNDA) seeking the approval of decitabine and cedazuridine (Inqovi) plus venetoclax (Venclexta) for the treatment of adult patients with newly diagnosed acute myeloid leukemia (AML) who are not eligible for intensive induction chemotherapy.¹

This submission was based on findings from the single-arm phase 2b ASCERTAIN-V trial (NCT04657081), which were presented at the 2025 ASCO Annual Meeting and the 2025 EHA Congress. ASCERTAIN-V investigated decitabine plus cedazuridine and venetoclax in 101 adult patients with newly diagnosed AML who were ineligible for intensive induction chemotherapy. At a median follow-up of 11.2 months, the trial met its primary end point, with a complete response (CR) rate of 46.5% (95% CI, 36.5%-56.7%) in the total population.^2,3 Additionally, the rate of CR/CR with incomplete hematologic recovery was 63.4% (95% CI, 53.2%-72.7%), and the rate of CR/CR with partial hematologic recovery was 51.5% (95% CI, 41.3%-61.6%). The estimated median overall survival was 15.5 months (95% CI, 7.6-not evaluable). At 12 months, the median duration of response was not reached, and 75.3% of patients who had achieved CR remained in CR.

Moreover, subgroup analyses showed consistent CR rates across prespecified patient subgroups. Notably, high CR rates were observed in patients younger than 76 years of age (57.9%; 95% CI, 33.5%-79.7%), as well as those with a baseline ECOG performance status of 0 (51.9%; 95% CI, 31.9%-71.3%). Additionally, the CR rate was 48.8% (95% CI, 37.9%-59.9%) among patients who had received no prior anticancer therapies.

“We have an unwavering dedication to developing innovative new cancer treatments, and the FDA’s acceptance of our sNDA for [decitabine plus cedazuridine] in combination with venetoclax highlights the need for novel approaches in AML,” Harold Keer, MD, PhD, chief medical officer of Taiho Oncology, stated in a news release.¹ “If approved for patients with AML who are not eligible to undergo intensive induction chemotherapy, [decitabine plus cedazuridine] in combination with venetoclax would offer the first all-oral alternative to current therapies.”

In ASCERTAIN-V, patients received decitabine plus cedazuridine on days 1 through 5 of each 28-day treatment cycle, in combination with daily venetoclax. Patients continued treatment until disease progression, unacceptable toxicity, or patient withdrawal from the study.²

Investigators reported no new safety concerns with the combination.^1-3 In total, 99.0% of patients experienced any adverse effects (AEs), 80.2% of patients experienced treatment-related AEs, 84.2% of patients experienced serious AEs, and 35.6% of patients experienced treatment-related serious AEs. Additionally, 98.0% of patients experienced grade 3 or higher AEs, the most common being febrile neutropenia (49.5%), anemia (38.6%), and neutropenia (35.6%). Other grade 3 or higher AEs included decreased platelet counts (24.8%), thrombocytopenia (19.8%), decreased neutrophil count (19.8%), decreased white blood cell counts (14.9%), and decreased appetite (1.0%).

AEs leading to treatment discontinuation (8.9%), treatment interruption (68.3%), and dose reduction (13.9%) were reported. At 30 days after the first dose of decitabine plus cedazuridine, 3 deaths were attributed to either AEs or disease progression; this number rose to 10 deaths at 60 days.

Notably, pharmacokinetic analyses confirmed that no drug-drug interactions occurred between decitabine/cedazuridine and venetoclax. Additionally, the pharmacokinetics of decitabine and cedazuridine were not affected by venetoclax.^2,3

Previously, decitabine plus cedazuridine was FDA approved in July 2020 for the treatment of adult patients with select subtypes of previously untreated de novo and secondary myelodysplastic syndromes, including those with chronic myelomonocytic leukemia.⁴

References

1. Taiho Oncology and Taiho Pharmaceutical announce U.S. FDA acceptance of supplemental new drug application for Inqovi in combination with venetoclax to treat patients with acute myeloid leukemia. News release. Taiho Oncology, Inc., and Taiho Pharmaceutical Co., Ltd. July 9, 2025. Accessed July 9, 2025. https://www.taihooncology.com/us/news/taiho-oncology-and-taiho-pharmaceutical-announce-us-fda-acceptance-of-supplemental-new-drug-application-for-inqovi-in-combination-with-venetoclax-to-treat-patients-with-acute-myeloid-leukemia/
2. Zeidan AM, Griffiths EA, Dinardo CD, et al. An all-oral regimen of decitabine-cedazuridine (DEC-C) plus venetoclax (VEN) in patients (pts) with newly diagnosed acute myeloid leukemia (AML) ineligible for intensive induction chemotherapy: results from a phase 2 cohort of 101 pts. J Clin Oncol. 2025;43(suppl 16):6504. doi: 10.1200/JCO.2025.43.16_suppl.6504
3. Roboz G, Zeidan AM, Mannis G, et al. All-oral decitabine-cedazuridine (Dec-C) + venetoclax (Cen) in patients with newly diagnosed acute myeloid leukemia (AML) ineligible for induction chemotherapy: phase 1/2 clinical trial results. Presented at: 2025 European Hematology Association Congress; June 12-15, 2025; Milan, Italy. Abstract S135.
4. FDA approves oral combination of decitabine and cedazuridine for myelodysplastic syndromes. FDA. July 7, 2020. Accessed July 9, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-oral-combination-decitabine-and-cedazuridine-myelodysplastic-syndromes