FDA Approves Decitabine/Cedazuridine Plus Venetoclax in Unfit AML

The FDA has approved the supplemental new drug application for the combination of decitabine and cedazuridine (Inqovi) plus venetoclax (Venclexta) for treatment of adult patients with newly diagnosed acute myeloid leukemia (AML) who are ineligible for intensive induction chemotherapy.¹ This landmark approval introduces an all-oral hypomethylating agent (HMA) and B-cell lymphoma 2 (BCL-2) inhibitor combination regimen for this high-risk patient population.

The FDA’s decision is supported by data from the international, single-arm, phase 2b ASCERTAIN-V trial (NCT04657081), which assessed the combination in 101 adults with newly diagnosed AML.² The study specifically enrolled a population representative of those deemed unfit for intensive chemotherapy, including older adults aged 75 years or older and those with comorbidities.

Here, the primary end point was achieved with a complete response (CR) rate of 46.5% (95% CI, 36.5%-56.7%).^3,4 The rate of CR with incomplete hematologic recovery was 63.4% (95% CI, 53.2%-72.7%).

Regarding other efficacy end points, the median overall survival was estimated at 15.5 months, while the median duration of response had not been reached by 12 months. Notably, approximately 75% of patients who achieved CR status remained in remission at 1 year.

Safety Profile

The safety profile of the all-oral regimen was manageable and consistent with the known toxicities of the individual agents, with no new safety concerns or drug-drug interactions observed between decitabine/cedazuridine and venetoclax.

Grade 3 or higher adverse events (AEs) occurred in 98% of patients, with the most frequent being hematologic toxicities such as febrile neutropenia (49.5%), anemia (38.6%), and neutropenia (35.6%). Early mortality was low, with 30-day and 60-day death rates due to AEs or disease progression at 3.0% and 9.9%, respectively.

About the Oral Combination

Decitabine/cedazuridine was originally approved by the FDA in July 2020 for the treatment of adult patients with myelodysplastic syndromes and chronic myelomonocytic leukemia,⁵ where it has continued to show high rates of response in high-risk patient populations. The combination utilizes cedazuridine to prevent the degradation of decitabine in the gut, allowing for therapeutic systemic levels of the HMA via oral delivery.

Venetoclax, a BCL-2 inhibitor, has been a cornerstone of AML therapy for patients ineligible for intensive chemotherapy since its accelerated approval in 2018.⁶ This latest approval marks the first time both components of the HMA/BCL-2 backbone are available in a single, oral-only administration schedule.

The recommended dosing regimen for the combination as evaluated in the ASCERTAIN-V trial includes 35 mg decitabine and 100 mg cedazuridine taken once daily on days 1 through 5 of each 28-day cycle, in conjunction with the established ramp-up and maintenance dosing of venetoclax at 400 mg daily thereafter.

REFERENCES

1. FDA approves oral combination of decitabine and cedazuridine tablets with venetoclax for newly diagnosed acute myeloid leukemia. News release. US FDA. May 13, 2026. Accessed May 13, 2026. https://tinyurl.com/59bz8j8d

2. Pharmacokinetics, safety, and efficacy of ASTX727 in combination with venetoclax in acute myeloid leukemia (AML). ClinicalTrials.gov. Updated December 8, 2025. Accessed January 27, 2026. https://clinicaltrials.gov/study/NCT04657081

3. 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. July 9, 2025. Accessed January 9, 2025. https://tinyurl.com/yn57e3rd

4. Roboz GJ, Zeidan AM, Mannis GN, 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. Presented at: European Hematology Association Congress; June 12-15, 2025; Milan, Italy. Abstract S135.

5. FDA approves oral combination of decitabine and cedazuridine for myelodysplastic syndromes. News release. FDA. July 7, 2020. Accessed January 27, 2026. https://tinyurl.com/46jrefjb

6. FDA approves venetoclax in combination for AML in adults. News release. FDA. December 14, 2018. Accessed January 27, 2026. https://tinyurl.com/bder6wpn