BOREAS: a global, phase III study of the MDM2 inhibitor navtemadlin (KRT-232) in relapsed/refractory myelofibrosis.
Srdan VerstovsekHaifa Kathrin Al-AliJohn O MascarenhasAndrew Charles PerkinsAlessandro Maria Maria VannucchiSanjay R MohanBart L ScottDariusz WoszczykSteffen KoschmiederRegina García-DelgadoRejtő LászlóJesse S McGreivyWayne P RothbaumJean-Jacques KiladjianPublished in: Future oncology (London, England) (2022)
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.
Keyphrases
- phase iii
- open label
- phase ii study
- placebo controlled
- double blind
- acute lymphoblastic leukemia
- clinical trial
- acute myeloid leukemia
- phase ii
- diffuse large b cell lymphoma
- multiple myeloma
- cell cycle arrest
- cell death
- hodgkin lymphoma
- wild type
- poor prognosis
- induced apoptosis
- oxidative stress
- randomized controlled trial
- anti inflammatory
- study protocol
- physical activity
- depressive symptoms
- locally advanced
- long non coding rna
- radiation therapy
- rectal cancer
- smoking cessation
- pi k akt
- combination therapy