In the first human clinical trial of an IDH1-mutant inhibitor, 17 patients with relapsed or refractory AML and IDH1 mutations were enrolled in one of four groups that received AG-120 (Agios Pharmaceuticals; Cambridge, MA) in escalating doses. The trial began in March 2014, and as of October 17, seven patients were responding to treatment, including four who experienced complete remissions; three had not yet been evaluated....Considering that some patients in the study experienced complete remission of their cancers, AG-120 may have potential to transform treatment for IDH1 mutant–positive AML…

To confirm TRK kinase targeting following entrectinib treatment, IMS-M2 or M0-91 cells were treated with serial dilutions of entrectinib in vitro and cell lysates were examined by immunoblotting….Entrectinib treatment at low nanomolar doses resulted in cell death in IMS-M2 and M0-91 cell lines....these data demonstrate that entrectinib treatment specifically inhibits in vitro proliferation and survival of ETV6–NTRK3 fusion–positive AML cell lines.