TP-0903 in TP53 Mutant or Complex Karyotype AML

Patients who have acute myeloid leukemia (AML) with mutant TP53 and/or complex karyotype have a dismal prognosis; frontline therapy for patients equal to or greater than 60 years old includes hypomethylating agent-based regimens, but outcomes are poor, and novel strategies are necessary to improve outcomes for these patients. Based on compelling preclinical data, we performed a phase 1b/2 study to evaluate the safety and efficacy of TP-0903, a multikinase inhibitor, in combination with a 10-day course of decitabine. The combination of TP-0903 and decitabine was well-tolerated and, despite substantial pharmacokinetic variability and relatively unselective kinase inhibition, TP-0903 had activity across two dose levels with an overall response rate (CR/CRh/CRi/MLFS) of 48.2% and median overall survival of 7.6 months, which is comparable to other emerging therapies. The collective data suggest TP-0903 may offer insight and serve as a benchmark for the development of future agents leveraging similar strategies or scaffolds to improve outcomes in these intractable subtypes of AML.