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Phase 2 study of bosutinib in Japanese patients with newly diagnosed chronic phase chronic myeloid leukemia

Abstract

This open-label, single-arm, phase 2 study (ClinicalTrials.gov, NCT03128411) evaluated the efficacy, safety, and pharmacokinetics of bosutinib at a starting dose of 400 mg once daily (QD) in Japanese patients with newly diagnosed chronic phase chronic myeloid leukemia (CP CML). The primary endpoint was major molecular response (MMR) at Month 12 in the modified as-treated population (Philadelphia chromosome-positive [Ph+] patients with e13a2/e14a2 transcripts). Sixty Japanese patients with CP CML were treated with bosutinib; median age was 55 years (range 20–83), 60.0% were males, and all were Ph+ and had e13a2/e14a2 transcripts. After median follow-up of 16.6 months (range 11.1–21.9), 41 (68.3%) patients remained on bosutinib. The MMR rate at Month 12 was 55.0% (2-sided 90% confidence interval: 44.4–65.6). There were no on-treatment transformations to accelerated/blast phase, and no patient died on treatment or within 28 days of the last bosutinib dose. The most common treatment-emergent adverse events were diarrhea (86.7%), increased alanine aminotransferase (55.0%), and increased aspartate aminotransferase (46.7%). The primary objective of this phase 2 study was met, and there were no new safety signals for bosutinib. These data suggest bosutinib is an effective first-line treatment option for Japanese patients with newly diagnosed CP CML.

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Upon request, and subject to certain criteria, conditions and exceptions (see https://www.pfizer.com/science/clinical-trials/trial-data-and-results for more information), Pfizer will provide access to individual de-identified participant data from Pfizer-sponsored global interventional clinical studies conducted for medicines, vaccines and medical devices (1) for indications that have been approved in the US and/or EU or (2) in programs that have been terminated (i.e., development for all indications has been discontinued). Pfizer will also consider requests for the protocol, data dictionary, and statistical analysis plan. Data may be requested from Pfizer trials 24 months after study completion. The de-identified participant data will be made available to researchers whose proposals meet the research criteria and other conditions, and for which an exception does not apply, via a secure portal. To gain access, data requestors must enter into a data access agreement with Pfizer.

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Acknowledgements

This study was sponsored by Pfizer. Medical writing support was provided by Joanna Bloom, PhD, of Engage Scientific Solutions and was funded by Pfizer.

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Correspondence to Masayuki Hino.

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Masayuki Hino reports research funding from Pfizer, Novartis, and Otsuka, and honoraria from Pfizer, Novartis, Otsuka, and Bristol-Myers Squibb. Itaru Matsumura reports research funding from Pfizer and Otsuka, speakers bureau with Novartis and Bristol-Myers Squibb, and consultancy with Otsuka. Shin Fujisawa reports honoraria and research funding from Novartis, Pfizer, Otsuka, and Bristol-Myers Squibb. Kenichi Ishizawa reports research funding from Pfizer and Otsuka and speakers bureau with Novartis and Bristol-Myers Squibb. Takaaki Ono reports honoraria from Celgene, Merck Sharp & Dohme, Ono, Novartis, Bristol-Myers Squibb, Pfizer, Otsuka, and Takeda and research funding from, Celgene, Merck Sharp & Dohme, Ono, Kyowa Hakko Kirin, and Chugai. Emiko Sakaida reports research funding from Bristol-Myers Squibb, Chugai, Ono, and Kyowa Kirin. Naohiro Sekiguchi reports research funding from Ono, A2 Healthcare, Astellas, Janssen, Merck Sharp & Dohme, Otsuka, Pfizer, PPD-SNBL, Sumitomo Dainippon Pharma, Daiichi Sankyo Company, and Bristol-Myers Squibb. Yusuke Tanetsugu, Kei Fukuhara, Masayuki Ohkura, and Yuichiro Koide report employment by Pfizer R&D Japan G.K. Naoto Takahashi reports research funding and honoraria from Pfizer, Otsuka, and Novartis, and research funding from Chugai, Eizai, Asahikasei, Ono, Kyowahakko-Kirin, and Toyamakagaku, outside the submitted work.

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Hino, M., Matsumura, I., Fujisawa, S. et al. Phase 2 study of bosutinib in Japanese patients with newly diagnosed chronic phase chronic myeloid leukemia. Int J Hematol 112, 24–32 (2020). https://doi.org/10.1007/s12185-020-02878-x

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  • DOI: https://doi.org/10.1007/s12185-020-02878-x

Keywords

  • Bosutinib
  • Tyrosine kinase inhibitor
  • Chronic myeloid leukemia
  • Japan