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

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

32 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
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 - 1 Dec 2022

Keywords

MDM2 inhibitor
myelofibrosis
myeloproliferative neoplasms
navtemadlin
p53

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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

@article{8ec924446aa14282b9abe30a1ad9607a,

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

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. .",

keywords = "MDM2 inhibitor, myelofibrosis, myeloproliferative neoplasms, navtemadlin, p53",

author = "Srdan Verstovsek and Al-Ali, \{Haifa Kathrin\} and John Mascarenhas and Andrew Perkins and Vannucchi, \{Alessandro Maria\} and Mohan, \{Sanjay R.\} and Scott, \{Bart L.\} and Dariusz Woszczyk and Steffen Koschmieder and Regina Garc{\'i}a-Delgado and Rejt{\AA}' L{\'a}szl{\'o} and McGreivy, \{Jesse S.\} and Rothbaum, \{Wayne P.\} and Kiladjian, \{Jean Jacques\}",

note = "Publisher Copyright: {\textcopyright} 2022 The Authors.",

year = "2022",

month = dec,

day = "1",

doi = "10.2217/fon-2022-0901",

language = "English",

volume = "18",

pages = "4059--4069",

journal = "Future Oncology",

issn = "1479-6694",

publisher = "Taylor and Francis Ltd.",

number = "37",

}

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

TY - JOUR

T1 - BOREAS

T2 - a global, phase III study of the MDM2 inhibitor navtemadlin (KRT-232) in relapsed/refractory myelofibrosis

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

PY - 2022/12/1

Y1 - 2022/12/1

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. .

KW - MDM2 inhibitor

KW - myelofibrosis

KW - myeloproliferative neoplasms

KW - navtemadlin

KW - p53

UR - https://www.scopus.com/pages/publications/85148375730

U2 - 10.2217/fon-2022-0901

DO - 10.2217/fon-2022-0901

M3 - Review article

C2 - 36416118

AN - SCOPUS:85148375730

SN - 1479-6694

VL - 18

SP - 4059

EP - 4069

JO - Future Oncology

JF - Future Oncology

IS - 37

ER -

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

Abstract

Keywords

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