CFI-400945 + azacitidine

CFI-400945 + azacitidine is a combination drug regimen under clinical investigation primarily for the treatment of acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and chronic myelomonocytic leukemia (CMML)[1][3][5][7]. CFI-400945 is a first-in-class, oral, small molecule inhibitor that selectively targets Polo-like kinase 4 (PLK4), a serine/threonine kinase crucial to centriole duplication, genomic integrity, and cell division[1][2][3][5]. PLK4 inhibition is hypothesized to cause mitotic catastrophe in tumor cells, particularly those with genomic instability. Azacitidine is a hypomethylating agent known to inhibit DNA methyltransferase, thereby inducing DNA hypomethylation and reactivating tumor suppressor genes. The combination is being evaluated for safety, tolerability, pharmacokinetics, and preliminary efficacy. This regimen is intended for relapsed/refractory and untreated patients ineligible for intensive therapy[1][3][5][7]. CFI-400945 was developed by Treadwell Therapeutics[3][5], and combination studies for AML, MDS, and CMML are ongoing.