Asciminib vs bosutinib in CML patients pretreated with ≥2 tyrosine kinase inhibitors: Results from the Japanese subgroup analysis of ASCEMBL study

Junichiro Yuda; Noriko Doki; Hiroshi Matsuoka; Takafumi Yokota; Akihiro Tomita; Naoto Takahashi; Itaru Matsumura; Kohmei Kubo; Tatsunori Goto; Keita Kirito; Akio Maki; Makoto Aoki; Alex Allepuz; Yosuke Minami

doi:10.1002/cam4.5212

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.

Authors

Junichiro Yuda¹, Noriko Doki², Hiroshi Matsuoka³, Takafumi Yokota⁴, Akihiro Tomita⁵, Naoto Takahashi⁶, Itaru Matsumura⁷, Kohmei Kubo⁸, Tatsunori Goto⁹, Keita Kirito¹⁰, Akio Maki¹¹, Makoto Aoki¹¹, Alex Allepuz¹², Yosuke Minami¹

Affiliations

¹ National Cancer Center Hospital East, Chiba, Japan.
² Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan.
³ Kobe University Hospital, Kobe, Japan.
⁴ Osaka University Hospital, Osaka, Japan.
⁵ Fujita Health University School of Medicine, Toyoake, Japan.
⁶ Akita University Hospital, Akita, Japan.
⁷ Kindai University Hospital, Osaka, Japan.
⁸ Aomori Prefectural Central Hospital, Aomori, Japan.
⁹ Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital, Nagoya, Japan.
¹⁰ University of Yamanashi Hospital, Yamanashi, Japan.
¹¹ Novartis Pharma KK, Tokyo, Japan.
¹² Novartis Pharma AG, Basel, Switzerland.

Abstract

Asciminib, a first-in-class, allosteric inhibitor of BCR-ABL1 that acts by STAMP (Specifically Targeting the ABL Myristoyl Pocket), is a novel therapeutic option for patients with chronic myeloid leukemia (CML). In the global, phase 3, open-label ASCEMBL study in patients with CML in chronic phase (CML-CP) pretreated with ≥2 tyrosine kinase inhibitors (TKIs) (NCT03106779), asciminib (40 mg twice-daily) demonstrated significant superiority over the ATP-competitive TKI bosutinib (500 mg once daily) for the primary endpoint of major molecular response (MMR; BCR::ABL1 transcript levels on the international scale [BCR::ABL1^IS ] ≤0.1%) at week 24. Here, we report results from a descriptive subgroup analysis of Japanese patients enrolled in ASCEMBL study (data cut-off: May 25, 2020). Overall, 16 Japanese patients were randomized (asciminib, n = 13; bosutinib, n = 3). At week 24, the MMR rate with asciminib was 30.8% (4/13; 95% confidence interval [CI], 9.09-61.43). BCR::ABL1^IS ≤1% and complete cytogenic response (CCyR) at week 24 were 61.5% (8/13 patients) and 50.0% (4/8 patients), respectively. In the bosutinib group, no patient achieved MMR, CCyR, or BCR::ABL1^IS ≤1%, but results were limited by the low number of patients. The safety profile of asciminib was comparable to that previously observed in the overall study population. Findings from this Japanese subgroup analysis of the ASCEMBL study support the use of asciminib for the treatment of Japanese patients with CML-CP previously treated with ≥2 TKIs. ClinicalTrials.gov Identifier: NCT03106779.

Keywords: ASCEMBL; BCR-ABL1 inhibitor; STAMP; asciminib; chronic myeloid leukemia; major molecular response; tyrosine kinase inhibitors.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

East Asian People
Fusion Proteins, bcr-abl
Humans
Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / drug therapy
Leukemia, Myeloid, Chronic-Phase* / drug therapy
Protein Kinase Inhibitors / therapeutic use
Tyrosine Kinase Inhibitors

Substances

asciminib
bosutinib
Tyrosine Kinase Inhibitors
Fusion Proteins, bcr-abl
Protein Kinase Inhibitors

Associated data

ClinicalTrials.gov/NCT03106779