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

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::ABL1IS ] ≤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::ABL1IS ≤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::ABL1IS ≤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.

Conflict of interest statement

Naoto Takahashi has received honoraria from Pfizer, Otsuka, and Novartis; research funding from Pfizer, Otsuka, Novartis, Chugai, Eizai, Asahikasei, Ono, and Kyowahakko‐Kirin outside the submitted work. Yosuke Minami received research funding from Ono and CMIC, and honoraria from Bristol‐Myers Squibb, Novartis, Astellas, and Daiichi‐Sankyo. Itaru Matsumura received honoraria from Novartis Pharma KK, Bristol‐Myers Squibb, Pfizer Japan Inc., Daiichi Sankyo Co Ltd., Otsuka Pharmaceutical Co Ltd., Astellas Pharma Inc., Amgen Astellas BioPharma K.K., Janssen Pharmaceutical K.K., AbbVie GK.; research funding from Chugai Pharmaceutical Co., Ltd., Novartis Pharma KK, AbbVie GK., Takeda Pharmaceutical Company Limited., Pfizer Japan Inc., Eisai Co., Ltd., Alexion, Asahikasei, Ono, Kyowahakko‐Kirin, Shionogi & Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Nippon Shinyaku Co., Ltd., Taiho Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Sanofi K.K., Astellas Pharma Inc., Otsuka Pharmaceutical Co., Ltd, MSD K.K., outside the submitted work. Hiroshi Matsuoka received research funding from Takeda Pharmaceutical Company Limited, Sysmex Corporation. Takafumi Yokota is an employee of Teijin Limited and received research funding from LUCA Science Inc. Akihiro Tomita received research funding from Perseus Proteomics Inc, Novartis Pharma K.K., Pfizer Japan Inc, Chugai Pharmaceutical Co., Ltd., Kyowa Kirin Ltd., Ono Pharmaceutical Co., Ltd., and Taiho Pharmaceutical Co., Ltd. Akio Maki, Makoto Aoki, and Alex Allepuz are employees of Novartis. Noriko Doki, Kohmei Kubo, Keita Kirito, Tatsunori Goto, and Junichiro Yuda have nothing to disclose.

© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Figures

FIGURE 1

ASCEMBL study design. CML‐CP, chronic myeloid leukemia in chronic phase; FPFV, First patient first visit; MCyR, major cytogenetic response; TKI, tyrosine kinase inhibitors. aPatients will continue to receive study treatment for up to 96 weeks after the last patient's first dose or 48 weeks after the last patient switches to asciminib, whichever is longer; bOption of switch to asciminib allowed only for patients meeting lack of efficacy criteria based on ELN 2013 recommendations; cSurvival follow‐up is not part of this report.

FIGURE 2

Efficacy endpoints at week 24 in Japanese patients randomized to Asciminib in the ASCEMBL study. aAmong patients without CCyR at baseline (n = 8); CCyR, complete cytogenetic response; IS, international scale; MMR, major molecular response (BCR::ABL1IS ≤0.1%). In the bosutinib group (n = 3), no patient achieved MMR, BCR::ABL1IS ≤1% or CCyR at week 24.