ASCERTAIN-V Data Support Oral HMA Combination as AML Frontline Option

Data from the phase 1/2 ASCERTAIN-V trial (NCT04657081), which supported the May 2026 FDA approval of oral decitabine/cedazuridine (DEC-C; Inqovi) plus venetoclax (Venclexta) in newly diagnosed acute myeloid leukemia (AML), showed a 63.4% complete response (CR) or CR with incomplete hematologic recovery (CRi) rate with the all-oral combination.^1,2 CancerNetwork® spoke with Courtney D. DiNardo, MD, MSCE, professor in the Department of Leukemia and Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center; and Michael R. Savona, MD, professor of internal medicine and cancer biology and director of the Hematologic Malignancies Research and Early Therapy Program at Vanderbilt University Medical Center, about whether these data make an oral hypomethylating agent (HMA) combination the immediate frontline default, or whether certain patients should still receive parenteral therapy.

Transcript:

CancerNetwork: The ASCERTAIN-V trial demonstrated a 63.4% CR/CRi rate using the all-oral combination. Are these data strong enough to make an oral HMA combination the immediate frontline default, or are there clinical subsets where you still favor parenteral delivery?

DiNardo: What the outcomes showed in the ASCERTAIN-V study is that the responses overlap with what you would expect with the parenteral form. There is no reason not to [adopt] the all-oral form just for the sake of convenience; it is telling you that this is an equivalent therapy. The only reason you would opt to go with the parenteral [form] is if you were concerned about the patient taking the pills as prescribed at home without supervision, or if it is just taking a while to get insurance approval. Oftentimes, I will start with the IV form for the first 1 to 2 cycles, often just the first, as I am waiting for that approval to come through and switch to oral [therapy] for subsequent cycles.

Savona: There are rare situations where people cannot take pills; that goes for any pill. There is nothing special about DEC-C that makes it difficult to absorb or raises particular drug-drug interaction [DDI] concerns; it is clean in that way. I will say that oral decitabine/cedazuridine only comes in 1 size: 35 mg/100 mg tablets, and dose reductions are done by number of days, not by dose. Even at the lower dose, we do find that people with a small body surface area can have profound cytopenia. That is something to consider when dosing these patients, and it does not change the fact that you would want to give it up front. There may be particularly brittle patients where you want to dial in more on [body surface area]. That instance will be rather uncommon and rare. And like Courtney, I agree this has basically demonstrated that this has made it to frontline therapy.

References

1. Roboz GJ, Zeidan AM, Mannis GN, et al. All-oral treatment of newly diagnosed acute myeloid leukemia. N Engl J Med. 2026;394(21):2107-2116. doi:10.1056/NEJMoa2510223
2. FDA approves oral combination of decitabine and cedazuridine tablets with venetoclax for newly diagnosed acute myeloid leukemia. News release. FDA. May 13, 2026. Accessed July 13, 2026. https://tinyurl.com/mv77f4fk