On May 13, the U.S. Food and Drug Administration (FDA) approved an oral combination of decitabine and cedazuridine tablets (Inqovi) plus venetoclax for the treatment of newly diagnosed acute myeloid leukemia (AML) in adults aged 75 years or older or who have comorbidities that preclude them from the use of intensive induction chemotherapy.
Study ASTX727-07
Efficacy for this combination regimen was evaluated in Study ASTX727-07 (ClinicalTrials.gov identifier NCT04657081), a single arm, open-label clinical trial of decitabine and cedazuridine tablets in combination with venetoclax in adults with newly diagnosed AML who were aged 75 years or older or who had comorbidities that precluded the use of intensive induction chemotherapy (n = 101). Efficacy was based on complete remission and the duration of complete remission, which was defined as the time from first complete remission until disease relapse or death from any cause, whichever occurred first.
When decitabine and cedazuridine tablets were combined with venetoclax, 42 patients achieved a complete remission (41.6%; 95% confidence interval [CI] = 31.9%–51.8%) with a median time to complete remission of 2 months (range = 0.4–15.3 months). The median duration of complete remission was not reached (range = 0.5–16.3 months).
The prescribing information includes warnings and precautions for myelosuppression and embryo-fetal toxicity.
Recommended Dosage
The recommended dose for decitabine and cedazuridine tablets in combination with venetoclax is one tablet (containing 35 mg decitabine and 100 mg cedazuridine) orally once daily on days 1 through 5 of each 28-day cycle until disease progression or unacceptable toxicity.
This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. For this review, the FDA collaborated with Health Canada. The applications may still be under review at the other regulatory agencies.
Decitabine and cedazuridine received Orphan Drug designation for this indication.
