Study of Efficacy of CML-CP Patients Treated With ABL001 Versus Bosutinib, Previously Treated With 2 or More TKIs

Summary

The purpose of this pivotal study was to compare the efficacy of asciminib (ABL001) with that of bosutinib in the treatment of patients with CML-CP having previously been treated with a minimum of two prior ATP-binding site TKIs. Patients intolerant to the most recent TKI therapy must have had BCR-ABL1 ratio \> 0.1% IS at screening and patients failing their most recent TKI therapy must have met the definition of treatment failure as per the 2013 European LeukemiaNet (ELN) recommendations. Patients with documented treatment failure as per 2013 ELN recommendations while on bosutinib treatment had the option to switch to asciminib treatment within 96 weeks after the last patient has been randomized on study.

Timeline

Start

2017-10-26

Primary completion

2020-05-25

Completion

2024-12-04

Outcome

Met primary endpoint

registry analysis (superiority test); Asciminib vs Bosutinib; p = 0.029; treatment difference in the MMR rate 12.2 (95% CI 2.19 to 22.30) NCT03106779 ↗

paper The MMR rate at week 24 was 25.5% with asciminib and 13.2% with bosutinib. PMID 34407542 ↗

release “Phase III ASCEMBL study met its primary endpoint of superiority in major molecular response rate at 24 weeks” novartis.com ↗

release “In the pivotal Phase III ASCEMBL trial, Scemblix demonstrated significant and clinically meaningful superiority in major molecular response (MMR) rate” novartis.com ↗

release “pivotal Phase III ASCEMBL trial, showing a near doubling in major molecular response rate for patients treated with Scemblix ® (asciminib) vs. Bosulif ® * (bosutinib)” novartis.com ↗

Publications

• Mauro MJ, Minami Y, Hochhaus A, Lomaia E, Voloshin S, Turkina A, Kim DW, Apperley JF, Cortes JE, Abdo A, Fogliatto LM, Kim DDH, le Coutre P, Saussele S, Annunziata M, Hughes TP, Chaudhri N, Chee L, Garcia-Gutierrez V, Sasaki K, Boquimpani C, Kapoor S, Espurz N, Dhamal V, Rea D. Asciminib remained superior vs bosutinib in late-line CML-CP after nearly 4 years of follow-up in ASCEMBL. Blood Adv. 2025 Aug 26;9(16):4248-4259. doi: 10.1182/bloodadvances.2025016042.
• Cortes JE, Rea D, Mauro MJ, Tran D, Wang P, Jadhav K, Yocolly A, Sasaki K. Health care resource utilization in 3L + patients with chronic phase chronic myeloid leukemia receiving asciminib or bosutinib. J Med Econ. 2023 Jan-Dec;26(1):915-923. doi: 10.1080/13696998.2023.2234776.
• Yuda J, Doki N, Matsuoka H, Yokota T, Tomita A, Takahashi N, Matsumura I, Kubo K, Goto T, Kirito K, Maki A, Aoki M, Allepuz A, Minami Y. Asciminib vs bosutinib in CML patients pretreated with >/=2 tyrosine kinase inhibitors: Results from the Japanese subgroup analysis of ASCEMBL study. Cancer Med. 2023 Feb;12(3):2990-2998. doi: 10.1002/cam4.5212. Epub 2022 Sep 27.
• Li YF, Combes FP, Hoch M, Lorenzo S, Sy SKB, Ho YY. Population Pharmacokinetics of Asciminib in Tyrosine Kinase Inhibitor-Treated Patients with Philadelphia Chromosome-Positive Chronic Myeloid Leukemia in Chronic and Acute Phases. Clin Pharmacokinet. 2022 Oct;61(10):1393-1403. doi: 10.1007/s40262-022-01148-9. Epub 2022 Jun 28.
• Rea D, Mauro MJ, Boquimpani C, Minami Y, Lomaia E, Voloshin S, Turkina A, Kim DW, Apperley JF, Abdo A, Fogliatto LM, Kim DDH, le Coutre P, Saussele S, Annunziata M, Hughes TP, Chaudhri N, Sasaki K, Chee L, Garcia-Gutierrez V, Cortes JE, Aimone P, Allepuz A, Quenet S, Bedoucha V, Hochhaus A. A phase 3, open-label, randomized study of asciminib, a STAMP inhibitor, vs bosutinib in CML after 2 or more prior TKIs. Blood. 2021 Nov 25;138(21):2031-2041. doi: 10.1182/blood.2020009984.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Asciminib	Unknown	40 mg	Oral
Comparator	Bosutinib	Small molecule	500 mg	Oral

Indications