FDA Approves Oral Decitabine/Cedazuridine With Venetoclax in Newly Diagnosed AML
核心洞察
The FDA approved oral decitabine and cedazuridine tablets (Inqovi, Taiho Oncology) with venetoclax for adults with newly diagnosed AML aged 75 or older or unfit for intensive induction chemotherapy.
Approval was based on the single-arm ASTX727-07 trial (NCT04657081) in 101 patients, which reported a complete remission rate of 41.6% and a median time to CR of 2 months.
The regimen is the first fully oral hypomethylating agent plus venetoclax combination for newly diagnosed AML, reviewed under Project Orbis with Health Canada and granted Orphan Drug Designation.
On May 13, the U.S. FDA granted approval to the oral combination of decitabine and cedazuridine tablets (Inqovi, Taiho Oncology, Inc.) with venetoclax for adults with newly diagnosed acute myeloid leukemia (搜索) (AML) who are aged 75 years or older or who have comorbidities making them ineligible for intensive induction chemotherapy.
Efficacy was evaluated in Study ASTX727-07 (NCT04657081), a single-arm, open-label trial of 101 patients with newly diagnosed AML who were ineligible for intensive induction chemotherapy. The complete remission rate was 41.6% (42/101 patients, 95% CI 31.9-51.8), with a median time to CR of 2 months (range 0.4-15.3 months) and median duration of CR not reached at the time of analysis (range 0.5-16.3 months). The approval was based on CR and duration of CR, defined as time from first documented CR until relapse or death from any cause. Prescribing information carries warnings and precautions for myelosuppression and embryo-fetal toxicity.
The recommended dose is one tablet containing 35 mg decitabine and 100 mg cedazuridine orally once daily on days 1-5 of each 28-day cycle, continued until disease progression or unacceptable toxicity, with venetoclax given per its prescribing guidelines. Decitabine inhibits DNA methyltransferases (搜索) to reactivate differentiation, apoptosis and cell-cycle genes, while cedazuridine is a cytidine deaminase (搜索) inhibitor that prevents degradation of oral decitabine in the gastrointestinal tract and liver, allowing systemic exposure comparable to intravenous decitabine. Venetoclax targets BCL-2 (搜索)-dependent leukemic cells by restoring mitochondrial apoptotic signaling. The FDA review was conducted under Project Orbis in collaboration with Health Canada, and the combination received Orphan Drug Designation for this AML indication.
Read the full article at OncoDaily.