TY - JOUR
T1 - A phase 3, open-label, randomized study of asciminib, a STAMP inhibitor, vs bosutinib in CML after 2 or more prior TKIs
AU - Réa, Delphine
AU - Mauro, Michael J.
AU - Boquimpani, Carla
AU - Minami, Yosuke
AU - Lomaia, Elza
AU - Voloshin, Sergey
AU - Turkina, Anna
AU - Kim, Dong Wook
AU - Apperley, Jane F.
AU - Abdo, Andre
AU - Fogliatto, Laura Maria
AU - Kim, Dennis Dong Hwan
AU - le Coutre, Philipp
AU - Saussele, Susanne
AU - Annunziata, Mario
AU - Hughes, Timothy P.
AU - Chaudhri, Naeem
AU - Sasaki, Koji
AU - Chee, Lynette
AU - García-Gutiérrez, Valentin
AU - Cortes, Jorge E.
AU - Aimone, Paola
AU - Allepuz, Alex
AU - Quenet, Sara
AU - Bédoucha, Véronique
AU - Hochhaus, Andreas
N1 - Funding Information:
The authors thank Rohini Roy and Karen Kaluza Smith (Nucleus Global) for medical editorial assistance with this manuscript. J.F.A. is grateful for the support of the Imperial National Institute for Health Research (NIHR) Oxford Biomedical Research Centre.
Funding Information:
The authors thank Rohini Roy and Karen Kaluza Smith (Nucleus Global) for medical editorial assistance with this manuscript. J.F.A. is grateful for the support of the Imperial National Institute for Health Research (NIHR) Oxford Biomedical Research Centre. The ASCEMBL study and work presented here were sponsored and funded by Novartis Pharmaceuticals Corporation. Financial support for medical editorial assistance was provided by Novartis.
Funding Information:
The ASCEMBL study and work presented here were sponsored and funded by Novartis Pharmaceuticals Corporation. Financial support for medical editorial assistance was provided by Novartis.
Publisher Copyright:
© 2021 American Society of Hematology
PY - 2021/11/25
Y1 - 2021/11/25
N2 - Patients with chronic myeloid leukemia in chronic phase (CML-CP) resistant/intolerant to ≥2 tyrosine kinase inhibitors (TKIs) are at high risk of experiencing poor outcomes because of disease biology and inadequate efficacy and/or safety of current therapies. Asciminib, a first-in-class BCR-ABL1 inhibitor Specifically Targeting the ABL Myristoyl Pocket (STAMP), has the potential to overcome resistance/intolerance to approved TKIs. In this phase 3, open-label study, patients with CML-CP previously treated with ≥2 TKIs were randomized (2:1) to receive asciminib 40 mg twice daily vs bosutinib 500 mg once daily. Randomization was stratified by major cytogenetic response (MCyR) status at baseline. The primary objective was to compare the major molecular response (MMR) rate at week 24 for asciminib vs bosutinib. A total of 233 patients were randomized to asciminib (n = 157) or bosutinib (n = 76). Median follow-up was 14.9 months. The MMR rate at week 24 was 25.5% with asciminib and 13.2% with bosutinib. The difference in MMR rate between treatment arms, after adjusting for MCyR at baseline, was 12.2% (95% confidence interval, 2.19-22.30; 2-sided P =.029). Fewer grade ≥3 adverse events (50.6% vs 60.5%) and adverse events leading to treatment discontinuation (5.8% vs 21.1%) occurred with asciminib than with bosutinib. The study showed a superior efficacy of asciminib compared with that of bosutinib, together with a favorable safety profile. These results support the use of asciminib as a new therapy in patients with CML-CP who are resistant/intolerant to ≥2 prior TKIs. This trial was registered at www.clinicaltrials.gov as #NCT03106779.
AB - Patients with chronic myeloid leukemia in chronic phase (CML-CP) resistant/intolerant to ≥2 tyrosine kinase inhibitors (TKIs) are at high risk of experiencing poor outcomes because of disease biology and inadequate efficacy and/or safety of current therapies. Asciminib, a first-in-class BCR-ABL1 inhibitor Specifically Targeting the ABL Myristoyl Pocket (STAMP), has the potential to overcome resistance/intolerance to approved TKIs. In this phase 3, open-label study, patients with CML-CP previously treated with ≥2 TKIs were randomized (2:1) to receive asciminib 40 mg twice daily vs bosutinib 500 mg once daily. Randomization was stratified by major cytogenetic response (MCyR) status at baseline. The primary objective was to compare the major molecular response (MMR) rate at week 24 for asciminib vs bosutinib. A total of 233 patients were randomized to asciminib (n = 157) or bosutinib (n = 76). Median follow-up was 14.9 months. The MMR rate at week 24 was 25.5% with asciminib and 13.2% with bosutinib. The difference in MMR rate between treatment arms, after adjusting for MCyR at baseline, was 12.2% (95% confidence interval, 2.19-22.30; 2-sided P =.029). Fewer grade ≥3 adverse events (50.6% vs 60.5%) and adverse events leading to treatment discontinuation (5.8% vs 21.1%) occurred with asciminib than with bosutinib. The study showed a superior efficacy of asciminib compared with that of bosutinib, together with a favorable safety profile. These results support the use of asciminib as a new therapy in patients with CML-CP who are resistant/intolerant to ≥2 prior TKIs. This trial was registered at www.clinicaltrials.gov as #NCT03106779.
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U2 - 10.1182/blood.2020009984
DO - 10.1182/blood.2020009984
M3 - Article
C2 - 34407542
AN - SCOPUS:85117286268
SN - 0006-4971
VL - 138
SP - 2031
EP - 2041
JO - Blood
JF - Blood
IS - 21
ER -