Taiho Oncology Highlights Promising Results of First All-Oral Treatment Regimen for Newly Diagnosed Acute Myeloid Leukemia
Taiho Oncology has announced the publication of important clinical trial findings in the prestigious New England Journal of Medicine, showcasing encouraging results from the ASCERTAIN-V Phase 1/2 study. The trial evaluated the first fully oral treatment regimen combining decitabine-cedazuridine and venetoclax in patients newly diagnosed with acute myeloid leukemia (AML) who are not candidates for intensive induction chemotherapy.
The publication marks a significant milestone in AML treatment research, as it introduces a potential alternative to traditional treatment approaches that often require frequent hospital visits for injections or intravenous infusions. The all-oral combination demonstrated promising response rates, durable remissions, and overall survival outcomes while maintaining a safety profile consistent with existing standard therapies.
Addressing an Important Need in AML Care
Acute myeloid leukemia is an aggressive cancer affecting the blood and bone marrow. In the United States alone, nearly 23,000 individuals are expected to receive an AML diagnosis in 2026. A substantial portion of these patients, particularly older adults and those with underlying health conditions, are unable to tolerate intensive induction chemotherapy, which remains a common frontline treatment approach.
For patients who cannot undergo intensive therapy, treatment generally involves a combination of venetoclax and hypomethylating agents such as decitabine or azacitidine. However, these regimens often require repeated injections or intravenous administration, resulting in frequent visits to healthcare facilities. Studies have shown that patients receiving these therapies may spend nearly 13 days each month attending treatment-related appointments, creating a significant burden on patients, caregivers, and healthcare systems.
The development of an all-oral regimen seeks to reduce these challenges by enabling patients to receive effective treatment while minimizing the need for repeated clinic visits.
Significance of Decitabine-Cedazuridine
The oral fixed-dose combination of decitabine and cedazuridine was developed to provide systemic exposure comparable to intravenous decitabine. Cedazuridine functions by inhibiting cytidine deaminase, an enzyme in the gut and liver that rapidly breaks down decitabine when taken orally. By blocking this enzyme, cedazuridine allows decitabine to remain active in the body, enabling effective oral administration.
This innovative approach creates the opportunity for patients to receive a hypomethylating agent through a convenient oral tablet while achieving similar therapeutic exposure to intravenous treatment.
Leadership Perspective
According to Dr. Harold Keer, Chief Medical Officer of Taiho Oncology, the company remains focused on developing therapies that improve outcomes and quality of life for patients living with cancer.
He emphasized that a fully oral treatment option could significantly reduce the logistical and financial burdens associated with repeated hospital and infusion-center visits. Such an approach may also offer greater flexibility and convenience for patients and caregivers managing long-term AML treatment.
Overview of the ASCERTAIN-V Trial
The ASCERTAIN-V study enrolled a total of 189 patients across multiple study phases, including 30 participants in Phase 1, 58 patients in Phase 2a, and 101 patients in Phase 2b.
Participants received treatment in 28-day cycles. Following an initial dose ramp-up period, patients were administered oral decitabine-cedazuridine during the first five days of each cycle and oral venetoclax on a daily basis. The study was designed to assess efficacy, safety, pharmacokinetics, and overall tolerability of the combination.
Researchers closely monitored patient responses, remission rates, survival outcomes, and treatment-related adverse events.
Encouraging Efficacy Results
Results from the Phase 2b portion of the study demonstrated meaningful clinical activity in patients with newly diagnosed AML who were ineligible for intensive chemotherapy.
The study reported a complete response rate of 47%, indicating that nearly half of participating patients achieved a full remission of detectable disease. When researchers combined complete responses with complete responses that included incomplete hematologic recovery, the overall response rate increased to 63%.
These findings suggest that the oral combination delivers efficacy comparable to established hypomethylating agent and venetoclax regimens currently used in clinical practice.
Another notable finding was the speed at which patients responded to treatment. The median time required to reduce bone marrow blast counts below 5% was only 28 days. Additionally, the median time to achieve either complete response or complete response with incomplete hematologic recovery was 35 days.
Rapid disease control is particularly important in AML, where delaying treatment responses can negatively affect outcomes.
Durable Remissions Observed
The trial also demonstrated encouraging durability of response among patients who achieved complete remission.
Among responding patients, 80% remained in remission six months after achieving a complete response. At twelve months, 75% of patients continued to maintain their remission status.
These findings indicate that responses achieved with the all-oral regimen can be sustained over extended periods, an important factor in improving long-term patient outcomes.
Survival Outcomes
Overall survival data from the study further supported the regimen’s clinical potential.
The median overall survival for patients enrolled in the Phase 2b cohort reached 15.5 months. Although longer follow-up is needed to fully evaluate long-term survival benefits, these results compare favorably with outcomes observed in similar patient populations receiving current standard therapies.
Early mortality rates were also relatively low. Thirty-day mortality was reported at 3%, while sixty-day mortality reached 10%. The median follow-up period for the study was 11.2 months.
Together, these findings suggest that the oral regimen can provide meaningful disease control while maintaining acceptable safety and tolerability.
Safety Profile Consistent with Existing Therapies
As expected for AML treatments involving hypomethylating agents and venetoclax, myelosuppression remained the most commonly observed side effect.
Serious adverse events were reported in 84% of patients, reflecting the complexity of treating AML in an older and medically vulnerable population. The most frequently reported Grade 3 or higher treatment-related adverse events included anemia, neutropenia, and febrile neutropenia.
Anemia occurred in approximately 30% of patients, while neutropenia was observed in 26%. Febrile neutropenia, a potentially serious complication involving low white blood cell counts accompanied by fever, affected 25% of participants.
Importantly, investigators found no evidence of drug-drug interactions between decitabine-cedazuridine and venetoclax, supporting the compatibility of the two medications when administered together.
Potential for Improved Treatment Management
An additional observation from the trial may have important implications for future treatment strategies.
Researchers adjusted treatment schedules after patients achieved clearance of leukemic blasts in the bone marrow. Once remission was established, the duration of venetoclax administration was reduced during subsequent treatment cycles.
This modification appeared to decrease rates of serious adverse events and febrile neutropenia. The findings suggest that an initial induction phase followed by individualized dose adjustments may help improve tolerability while maintaining therapeutic effectiveness.
Such an approach could reduce treatment-related complications and improve overall quality of life for patients receiving long-term therapy.
Expert Perspective
Dr. Gail J. Roboz, lead author of the publication and a leading leukemia specialist at Weill Cornell Medicine and NewYork-Presbyterian/Weill Cornell Medical Center, highlighted the significance of the findings.
According to Dr. Roboz, the combination’s positive efficacy, safety, pharmacokinetic, and tolerability results indicate that the regimen has the potential to become a meaningful alternative to current treatment approaches that rely on injectable or intravenous hypomethylating agents.
She noted that clinicians and patients have long anticipated a fully oral AML treatment option capable of delivering outcomes comparable to established therapies while offering greater convenience and flexibility.
The publication of the ASCERTAIN-V results in the New England Journal of Medicine represents an important advancement in AML treatment research. By demonstrating that a fully oral regimen can achieve strong response rates, durable remissions, and encouraging survival outcomes, the study opens the door to a new treatment paradigm for patients who are unable to undergo intensive chemotherapy.
As additional research and longer-term follow-up continue, the decitabine-cedazuridine plus venetoclax regimen may emerge as a valuable treatment option that reduces healthcare burdens while maintaining clinical effectiveness. For thousands of AML patients each year, particularly older adults and those with significant health challenges, this innovative all-oral approach could offer a more convenient and patient-centered pathway to care.
About Decitabine and Cedazuridine Fixed-Dose Combination
This product is an orally administered, fixed dose combination of the approved anti-cancer DNA hypomethylating agent, decitabine, together with cedazuridine,6 an inhibitor of cytidine deaminase.7 By inhibiting cytidine deaminase in the gut and the liver, the fixed dose combination is designed to allow for oral delivery of decitabine over five days in a given cycle to achieve comparable systemic exposure to IV decitabine administered over five days.
The mission of Taiho Oncology, Inc. is to improve the lives of patients with cancer, their families and their caregivers. The company specializes in the development and commercialization of orally administered anti-cancer agents for various tumor types. Taiho Oncology has a robust pipeline of small-molecule clinical candidates targeting solid-tumor and hematological malignancies, with additional candidates in pre-clinical development. Taiho Oncology is a subsidiary of Taiho Pharmaceutical Co., Ltd. which is part of Otsuka Holdings Co., Ltd. Taiho Oncology is headquartered in Princeton, New Jersey and oversees its parent company’s European and Canadian operations, which are located in Baar, Switzerland and Oakville, Ontario, Canada.
