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

doi:10.2217/fon-2022-0901

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

Leukemia

Research output: Contribution to journal › Review article › peer-review

11 Scopus citations

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 language	English (US)
Pages (from-to)	4059-4069
Number of pages	11
Journal	Future Oncology
Volume	18
Issue number	37
DOIs	https://doi.org/10.2217/fon-2022-0901
State	Published - Dec 1 2022

Keywords

MDM2 inhibitor
myelofibrosis
myeloproliferative neoplasms
navtemadlin
p53

ASJC Scopus subject areas

Oncology
Cancer Research

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10.2217/fon-2022-0901

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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. J. (2022). BOREAS: a global, phase III study of the MDM2 inhibitor navtemadlin (KRT-232) in relapsed/refractory myelofibrosis. Future Oncology, 18(37), 4059-4069. https://doi.org/10.2217/fon-2022-0901

Verstovsek, S, Al-Ali, HK, Mascarenhas, J, Perkins, A, Vannucchi, AM, Mohan, SR, Scott, BL, Woszczyk, D, Koschmieder, S, García-Delgado, R, László, R, McGreivy, JS, Rothbaum, WP & Kiladjian, JJ 2022, 'BOREAS: a global, phase III study of the MDM2 inhibitor navtemadlin (KRT-232) in relapsed/refractory myelofibrosis', Future Oncology, vol. 18, no. 37, pp. 4059-4069. https://doi.org/10.2217/fon-2022-0901

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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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AU - Verstovsek, Srdan

AU - Al-Ali, Haifa Kathrin

AU - Mascarenhas, John

AU - Perkins, Andrew

AU - Vannucchi, Alessandro Maria

AU - Mohan, Sanjay R.

AU - Scott, Bart L.

AU - Woszczyk, Dariusz

AU - Koschmieder, Steffen

AU - García-Delgado, Regina

AU - László, RejtÅ'

AU - McGreivy, Jesse S.

AU - Rothbaum, Wayne P.

AU - Kiladjian, Jean Jacques

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N2 - 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. .

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

Abstract

Keywords

ASJC Scopus subject areas

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