A phase 3, open-label, randomized study of asciminib, a STAMP inhibitor, vs bosutinib in CML after 2 or more prior TKIs.

Susanne Saussele, Andreas Hochhaus, Véronique Bédoucha, Sara Quenet, Alex Allepuz, Paola Aimone, Jorge E Cortes, Valentin García-Gutiérrez, Lynette Chee, Koji Sasaki, Naeem Chaudhri, Timothy P Hughes, Mario Annunziata, Delphine Réa, Philipp le Coutre, Dennis Dong Hwan Kim, Laura Maria Fogliatto, Andre Abdo, Jane F Apperley, Dong-Wook Kim, Anna Turkina, Sergey Voloshin, Elza Lomaia, Yosuke Minami, Carla Boquimpani, Michael J Mauro

Journal: Blood 2021;138(21):2031-2041

PMID: 34407542

Free Full Text on Elsevier Science View on PubMed

Abstract

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.

Address: DMU Hématologie, Hôpital Saint-Louis, Paris, France.; Myeloproliferative Neoplasms Program, Memorial Sloan Kettering Cancer Center, New York, NY.; HEMORIO, State Institute of Hematology Arthur de Siquiera Cavalcanti, Rio de Janeiro, Brazil.; Oncoclínica Centro de Tratamento Oncológico, Rio de Janeiro, Brazil.; Department of Hematology, National Cancer Center Hospital East, Kashiwa, Japan.; Institute of Oncology and Hematology, Almazov National Medical Research Centre, St Petersburg, Russia.; Hematology and Bone Marrow Transplantation, Russian Research Institute of Hematology and Transfusiology, St Petersburg, Russia.; Scientific and Advisory Department of Hemotherapy of Myeloproliferative Disorders, National Research Center for Hematology, Moscow, Russia.; Hematologic Tumor Medicine Department, Uijeongbu Eulji Medical Center, Eulji University, Uijeongbu, South Korea.; Department of Immunology and Inflammation, Centre for Haematology Imperial College London, London, United Kingdom.; Hemato-Oncology Department, Instituto do Câncer do Estado de São Paulo (ICESPSP), São Paulo, Brazil.; Hematology and Hemotherapy Department, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil.; Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Canada.; Department of Oncology and Hematology, Charité-Universitätsmedizin Berlin, Berlin, Germany.; Department of Haematology and Oncology, III. Medizinische Klinik, Medizinische Fakultät Mannheim der Universität Heidelberg, Mannheim, Germany.; Division of Hematology, AORN Cardarelli, Naples, Italy.; South Australian Health and Medical Research Institute and University of Adelaide, Adelaide, Australia.; Hematology, Stem Cell Transplant and Cellular Therapy Section, King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia.; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.; Haematology Department, Peter MacCallum Cancer Center-The Royal Melbourne Hospital, Melbourne, Australia.; Servicio de Hematología, Hospital Universitario Ramón y Cajal (IRYCIS), Madrid, Spain.; Georgia Cancer Center, Augusta, GA.; Novartis Pharma AG, Basel, Switzerland; and.; Department of Hematology and Internal Oncology, Universitätsklinikum Jena, Jena, Germany.

DOI: 10.1182/blood.2020009984

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MeSH Terms: Adult, Aged, Aged, 80 and over, Aniline Compounds, Antineoplastic Agents, Female, Humans, Leukemia, Myeloid, Chronic-Phase, Male, Middle Aged, Niacinamide, Nitriles, Protein Kinase Inhibitors, Pyrazoles, Quinolines, Treatment Outcome, Young Adult