BOREAS: A Global, Phase III Study of the MDM2 Inhibitor Navtemadlin (KRT-232) in Relapsed/Refractory Myelofibrosis

Patients with myelofibrosis (MF) who discontinue ruxolitinib due to progression/resistance have poor prognoses. JAK inhibitors control symptoms and reduce spleen volumes with limited impact on underlying disease pathophysiology. Murine double minute 2 (MDM2), a negative regulator of p53, is overexpressed in circulating malignant CD34⁺ MF cells. The oral MDM2 inhibitor navtemadlin (KRT-232) restores p53 activity to drive apoptosis of wild-type <i>TP53</i> tumor cells by inducing expression of pro-apoptotic Bcl-2 family proteins. Navtemadlin demonstrated promising clinical and disease-modifying activity and acceptable safety in a phase II study in patients with relapsed/refractory MF. The randomized phase III BOREAS study compares the efficacy and safety of navtemadlin to best available therapy in patients with MF that is relapsed/refractory to JAK inhibitor treatment.