AML Treatment Could Soon Get an All-Oral Option

FDA is reviewing a drug combination for acute myeloid leukemia patients ineligible for intensive chemotherapy.

A potential new treatment option is on the horizon for acute myeloid leukemia (AML) patients who cannot undergo intensive induction chemotherapy. The FDA is currently reviewing a drug combination that could offer an all-oral alternative.

Key Development

The FDA has accepted a supplemental new drug application (sNDA) for decitabine and cedazuridine (Inqovi) plus venetoclax (Venclexta). This combination targets adult patients newly diagnosed with AML who are not candidates for intensive induction chemotherapy.

The sNDA submission relies on data obtained from the phase 2b ASCERTAIN-V trial (NCT04657081). The results were presented at the 2025 ASCO Annual Meeting and the 2025 EHA Congress.

ASCERTAIN-V assessed the efficacy of decitabine plus cedazuridine combined with venetoclax in 101 adult patients with newly diagnosed AML who were ineligible for intensive induction chemotherapy. After a median follow-up of 11.2 months, the trial achieved its primary endpoint, demonstrating a complete response (CR) rate of 46.5% (95% CI, 36.5%-56.7%) across the entire group.

In addition, the CR/CR rate coupled with incomplete hematologic recovery reached 63.4% (95% CI, 53.2%-72.7%), and the CR/CR rate alongside partial hematologic recovery was 51.5% (95% CI, 41.3%-61.6%). The median overall survival was estimated at 15.5 months (95% CI, 7.6-not evaluable). At the one-year mark, the median duration of response was not reached, and 75.3% of patients who had achieved CR remained in CR.

Subgroup analyses revealed consistent CR rates across defined patient subgroups. High CR rates were seen in patients under 76 years old (57.9%; 95% CI, 33.5%-79.7%) and those with a baseline ECOG performance status of 0 (51.9%; 95% CI, 31.9%-71.3%). Among patients who had not received prior anticancer therapies, the CR rate stood at 48.8% (95% CI, 37.9%-59.9%).

“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,” stated Harold Keer, MD, PhD, chief medical officer of Taiho Oncology, in a news release.

Keer also noted, “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.”

Treatment Regimen and Safety Profile

During the ASCERTAIN-V trial, patients received decitabine plus cedazuridine on days 1 through 5 of each 28-day treatment cycle, along with daily venetoclax. Treatment continued until disease progression, unacceptable toxicity, or patient withdrawal.

Investigators reported no new safety concerns associated with the combination therapy. Overall, 99.0% of patients experienced adverse effects (AEs), 80.2% experienced treatment-related AEs, 84.2% experienced serious AEs, and 35.6% experienced treatment-related serious AEs. Grade 3 or higher AEs were seen in 98.0% of patients, with febrile neutropenia (49.5%), anemia (38.6%), and neutropenia (35.6%) being the most common.

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 led to treatment discontinuation (8.9%), treatment interruption (68.3%), and dose reduction (13.9%). Within 30 days of the first dose, 3 deaths were linked to AEs or disease progression; this number increased to 10 deaths within 60 days.

Pharmacokinetic analyses confirmed the absence of drug-drug interactions between decitabine/cedazuridine and venetoclax. Furthermore, venetoclax did not affect the pharmacokinetics of decitabine and cedazuridine.

Previous Approvals

The FDA previously approved decitabine plus cedazuridine in July 2020 for treating adult patients with specific subtypes of previously untreated de novo and secondary myelodysplastic syndromes, including chronic myelomonocytic leukemia.

In the United States, it is estimated that 6,000 new cases of AML will be diagnosed in 2024, with most patients being over 60 years old (American Cancer Society).