: 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 TP53 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.
BOREAS: a global, phase III study of the MDM2 inhibitor navtemadlin (KRT-232) in relapsed/refractory myelofibrosis / Verstovsek, S., Al-Ali, H.K., Mascarenhas, J., Perkins, A., Vannucchi, A.M., Mohan, S.R., Scott, B.L., Woszczyk, D., Koschmieder, S., García-Delgado, R., László, R., McGreivy, J.S., Rothbaum, W.P., Kiladjian, J.. - In: FUTURE ONCOLOGY. - ISSN 1744-8301. - ELETTRONICO. - (2022), pp. 4059-4069. [10.2217/fon-2022-0901]
BOREAS: a global, phase III study of the MDM2 inhibitor navtemadlin (KRT-232) in relapsed/refractory myelofibrosis
Vannucchi, Alessandro Maria;
2022
Abstract
: 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 TP53 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.
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