BOREAS: A Global, Phase III Study of the MDM2 Inhibitor Navtemadlin (KRT-232) in Relapsed/Refractory Myelofibrosis
Year: 2022
Type: review
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. Clinical Trial Registration: NCT03662126 (ClinicalTrials.gov).
Source: Future Oncology
Institutions: The University of Texas MD Anderson Cancer Center, University Hospital in Halle, Icahn School of Medicine at Mount Sinai, Monash University, University of Florence, Vanderbilt University Medical Center, Fred Hutch Cancer Center, University of Opole, RWTH Aachen University, Hospital Clínico Universitario Virgen de la Victoria, Kartos Therapeutics, Inc. (United States), Université Paris Cité, Hôpital Saint-Louis
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W4309728705