Data from the ongoing phase I Zella 101 study evaluating the safety and clinical activity of alvocidib, a potent CDK9 inhibitor, in combination with cytarabine and daunorubicin in patients with newly diagnosed acute myeloid leukemia (AML), was recently presented for the first time at the 24th Congress of the European Hematology Association (EHA).
Preliminary data from the study indicated that alvocidib in combination with cytarabine and daunorubicin has shown clinical activity with acceptable safety in patients with newly diagnosed AML. Of the 18 evaluable patients, more than three-quarters (78%, n=14) achieved a complete remission (CR) or complete remission with incomplete hematologic recovery (CRi). Of these patients attaining a CR/CRi, 78 percent (n=11) reached the 30-day post-study evaluation, per the study protocol. A subset of these patients, 27 percent (n=3 of 11) proceeded to stem cell transplant.
Additionally, among adverse cytogenic risk patients (n=9) who generally respond poorly to induction therapy, two-thirds (67%, n=6 of 9), achieved a CR/Cri (Abstract PF285). Of the patients that attained a CR/CRi (n=14), 10 (71%) are still in remission with a median follow-up of 76 days. In addition, 21 of 22 (95%) enrolled patients are still alive, with a median follow-up of 70 days.
Adverse events in the study include diarrhea, tumor lysis syndrome, infections and elevated AST levels and were consistent with those noted in previous alvocidib studies.
Alvocidib is an investigational small molecule inhibitor of cyclin-dependent kinase 9 (CDK9) currently being evaluated in a phase II study, Zella 201, in patients with relapsed or refractory MCL-1 dependent AML in combination with cytarabine and mitoxantrone (NCT02520011). Alvocidib is also being evaluated in Zella 101, a phase I clinical study evaluating the maximum tolerated dose, safety, and clinical activity of alvocidib in combination with (7+3) in newly diagnosed patients with AML (NCT03298984), and Zella 102, a phase Ib/II study in patients with myelodysplastic syndromes in combination with decitabine (NCT03593915). In addition, alvocidib is being evaluated in a phase I study in patients with relapsed or refractory AML in combination with venetoclax (NCT03441555).