FDA Approves Decitabine/Cedazuridine Plus Venetoclax in Newly Diagnosed AML

The FDA has approved decitabine and cedazuridine (Inqovi) in combination with venetoclax (Venclexta) for the treatment of adult patients with newly diagnosed acute myeloid leukemia (AML) who are at least 75 years of age or who have comorbidities that preclude the use of intensive induction chemotherapy.¹

The regulatory decision is supported by findings from the phase 2 ASCERTAIN-V study (NCT04657081), which showed that patients treated with the combination achieved a complete response (CR) rate of 41.6% (95% CI, 31.9%-51.8%) with a median time to CR of 2 months (range, 0.4-15.3 months). The median duration of CR was not reached (range, 0.5-16.3 months).

Additional results from ASCERTAIN-V were shared during the 2025 ASCO Annual Meeting² and the 2025 EHA Congress.³ At a median follow-up of 11.2 months, the regimen elicited a complete response (CR) rate of 46.5% (95% CI, 36.5%-56.7%);² the CR/CR with incomplete hematologic recovery rate was 63.4% (95% CI, 53.2%-72.7%) and the CR/CR with partial hematologic recovery rate was 51.5% (95% CI, 41.3%-61.6%). The median time to CR was 2.4 months. Of those who achieved a CR, 80.0% continued to respond for 6 months, and 75.3% continued to respond for 12 months. The median overall survival with the combination was 15.5 months (95% CI, 7.6-not estimable).

What is the design of ASCERTAIN-V trial examining decitabine/cedazuridine plus venetoclax in AML?

For phase 2 part B of the trial, decitabine and cedazuridine were administered on days 1 to 5 of every 28-day treatment cycle.² In cycle 1, venetoclax was given at a ramp-up dose of 100 mg on day 1, 200 mg on day 2, 400 mg on days 3 to 5, and 400 mg on days 6 to 28. For cycles 2 and 3, decitabine and cedazuridine continued to be given on days 1 to 5. Venetoclax was given at a dose of 400 mg for days 1 to 28. Treatment continued until disease progression, unacceptable toxicity, or study withdrawal.

The median patient age was 78 years (range, 63-88), with 81.2% aged 75 years or older. Most patients were male (60.4%), and approximately half (51.5%) had an ECOG performance status of 1. In terms of cytogenetic risk, which was classified per European Leukemia Net 2017 criteria, patients had favorable-risk disease (31.7%), intermediate-risk disease (33.7%), or adverse-risk disease (29.7%). Moreover, 16.8% of patients had tumors with TP53 mutations.

What was the safety profile of decitabine/cedazuridine plus venetoclax in this population of patients with AML?

Any adverse effects (AEs) occurred in 99.0% of patients (n = 101), with 80.2% being related to treatment. Serious toxicities were reported in 84.2% of patients, with 35.6% related to treatment. Grade 3 or higher AEs were experienced by 98.0% of patients; 72.3% of these effects were related to treatment. The most common TRAEs reported with the regimen were anemia (all grade, 32.7%; grade ≥ 3, 29.7%), decreased platelet count (26.7%; 24.8%), neutropenia (25.7%; 25.7%), febrile neutropenia (24.8%; 24.8%), thrombocytopenia (21.8%; 19.8%), decreased neutrophil count (20.8%; 19.8%), nausea (19.8%; 0%), decreased appetite (17.8%; 1.0%), and decreased white blood cell count (14.9%; 14.9%).

AEs resulted in dose reduction or treatment interruption for 13.9% and 68.3% of patients, respectively. Moreover, AEs led to treatment discontinuation for 8.9% of patients; AEs proved to be fatal for 15.8% of patients.

What is the significance of the approval?

In a recent Rapid Readouts program4 on ASCERTAIN-V, Amer Zeidan, MBBS, of Yale School of Medicine, in New Haven, Connecticut, said: “In newly diagnosed patients with AML ineligible for intensive chemotherapy, the all-oral regimen of decitabine/cedazuridine plus venetoclax represents a potential new standard of care.”

Check out the video below for additional expert insights about the significance of this approval from Courtney D. DiNardo, MD, MSCE, of The University of Texas MD Anderson Cancer Center in Houston.

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 February 23, 2026. 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. Zeidan A. An all-oral regimen of decitabine-cedazuridine (DEC-C) plus venetoclax (VEN) in patients with newly diagnosed AML ineligible for intensive induction chemotherapy: Results from a phase 2 cohort of 101 patients. OncLive.com. June 19, 2025. Accessed February 23, 2026. https://www.onclive.com/view/6504---an-all-oral-regimen-of-decitabine-cedazuridine-dec-c-plus-venetoclax-ven-in-patients-with-newly-diagnosed-aml-ineligible-for-intensive-induction-chemotherapy-results-from-a-phase-2-cohort-of-101-pts-