Oral Azacitidine-Cedazuridine Meets Pharmacokinetic Goal in Phase 3 MDS/CMML Trial

Oral azacitidine and cedazuridine (ASTX030) achieved its primary pharmacokinetic end point in patients with myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML), according to topline results from the phase 3 portion of the AZTOUND trial (NCT04256317).¹

In the randomized, open-label, crossover trial, the primary end point was total cycle area under the curve from 0 to 24 hours (AUC0-24), measured as the ratio of azacitidine total cycle AUC0-24 exposure following oral azacitidine and cedazuridine compared with subcutaneous (SC) azacitidine (Vidaza). According to Taiho Oncology, the safety profile observed with the oral regimen was also consistent with that of parenteral azacitidine.

“The positive topline results of the Phase 3 AZTOUND trial support the potential of an all-oral regimen of azacitidine and cedazuridine to meet the treatment needs of patients with MDS and CMML without the time and treatment burden associated with parenteral therapies,” Harold Keer, MD, PhD, chief medical officer of Taiho Oncology, stated in the news release. “We look forward to pursuing regulatory approval of oral azacitidine and cedazuridine to potentially bring this treatment option to patients.”

Background and Trial Design

ASTX030 is an investigational oral combination of the approved DNA methyltransferase inhibitor azacitidine and cedazuridine, a cytidine deaminase inhibitor designed to keep azacitidine active in the body without degradation. An oral combination of decitabine and cedazuridine (Inqovi) was approved for MDS in 2020 and for acute myeloid leukemia (AML) on May 13, 2026.

The AZTOUND trial included phase 1, 2, and 3 portions with ASTX030 monotherapy and phase 1 and 2 in combination with venetoclax (Venclexta) in treatment-naive AML. The AZTOUND trial’s phase 3 portion enrolled 88 adults with MDS or CMML to evaluate the pharmacokinetic exposure, safety, and efficacy of the oral combination against subcutaneous azacitidine. Patients were randomly assigned to received ASTX030 in cycle 1, followed by SC azacitidine in cycle 2, or the reverse, with all patients receiving ASTX030 in cycle 3 and onward.²

Phase 1 and 2 Findings

Phase 1 results demonstrated that ASTX030 was well tolerated with comparable safety to parenteral azacitidine, with a dose of 140/20-mg azacitidine/cedazuridine selected as the recommended phase 2 dose.³

In the phase 2 monotherapy portion of the trial, patients with MDS, CMML, and AML were treated with this dose, confirming a geometric mean ratio (GMR) for the primary pharmacokinetic end point of 0.913 (90% CI, 0.78-1.07) and suggesting body surface area–based dosing could ensure a more optimal dose aligned with the exposure achieved with subcutaneous azacitidine; investigators stated this was being incorporated into the phase 3 AZTOUND study. The most common treatment-emergent adverse events (TEAEs) were nausea, constipation, and fatigue; the most common TEAEs of grade 3 or higher included thrombocytopenia, neutropenia, and anemia.

Regulatory Path Forward

Based on the AZTOUND topline results, Taiho Oncology said it intends to submit a new drug application to the FDA seeking approval of the oral regimen for adults with MDS or CMML, and the company plans to submit the full trial results for presentation at an international medical conference.¹

Parenteral azacitidine requires ongoing infusion-center visits. Taiho stated that the all-oral azacitidine-cedazuridine regimen could be a way to reduce treatment burden for patients with MDS or CMML who currently rely on subcutaneous or intravenous administration.

“We believe the positive topline results of the AZTOUND phase 3 trial mark a key milestone in our collective efforts to develop a portfolio of novel treatments that improve clinical outcomes and quality of life for people with hematological malignancies,” Fabio Benedetti, MD, global chief medical officer of Taiho Pharmaceutical, stated in the news release. “We are grateful to the patients, caregivers and investigators participating in the AZTOUND trial and remain committed to advancing azacitidine and cedazuridine for patients with MDS and CMML.”

REFERENCES

1. Taiho Oncology and Taiho Pharmaceutical Announce Positive Topline Results in Phase 3 AZTOUND Trial Evaluating Oral Azacitidine and Cedazuridine in Myelodysplastic Syndromes or Chronic Myelomonocytic Leukemia. News release. Taiho Oncology, Inc., and Taiho Pharmaceutical Co., Ltd. October 1, 2026. Accessed October 1, 2026. https://tinyurl.com/2s3kfzrz

2. A Multi-phase Study of ASTX030 (Azacitidine and Cedazuridine) in Myeloid Neoplasm Alone or in Combination With Venetoclax in AML (AZTOUND Study). ClinicalTrials.gov. Updated April 30, 2026. Accessed October 1, 2026. https://clinicaltrials.gov/study/NCT04256317

3. Garcia-Manero G, Borate U, Brunner A, et al. A phase 2 dose confirmation trial of oral ASTX030, a combination of oral azacitidine with cedazuridine among patients with myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myeloid leukemia. Blood. 2025;146(suppl 1):491. doi:10.1182/blood-2025-491