BOREAS: a global, phase III study of the MDM2 inhibitor navtemadlin (KRT-232) in relapsed/refractory myelofibrosis

Srdan Verstovsek, Haifa Kathrin Al-Ali, John Mascarenhas, Andrew Perkins, Alessandro Maria Vannucchi, Sanjay R. Mohan, Bart L. Scott, Dariusz Woszczyk, Steffen Koschmieder, Regina García-Delgado, RejtÅ' László, Jesse S. McGreivy, Wayne P. Rothbaum, Jean Jacques Kiladjian

Research output: Contribution to journalReview ArticleOtherpeer-review

12 Citations (Scopus)

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. .

Original languageEnglish
Pages (from-to)4059-4069
Number of pages11
JournalFuture Oncology
Volume18
Issue number37
DOIs
Publication statusPublished - 1 Dec 2022

Keywords

  • MDM2 inhibitor
  • myelofibrosis
  • myeloproliferative neoplasms
  • navtemadlin
  • p53

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