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A phase I, dose-escalation study of oral PIM447 in Japanese patients with relapsed and/or refractory multiple myeloma

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Abstract

PIM447, a pan-proviral integration site for Moloney leukemia (PIM) kinase inhibitor, has shown preclinical activity in multiple myeloma (MM). This phase I, open-label, multicenter, dose-escalation study aimed to determine the maximum tolerated dose (MTD) and recommended dose for expansion (RDE) of PIM447 in Japanese patients with relapsed and/or refractory (R/R) MM. The study included 13 patients (250 mg once daily (QD), [n = 7]; 300 mg QD, [n = 6]). The sole dose-limiting toxicity observed was grade 3 QTc prolongation in one patient from the 300 mg group, and the MTD and RDE was not determined. The most common suspected PIM447-related adverse events (AEs) included thrombocytopenia (76.9%), anemia (53.8%), and leukopenia (53.8%). All patients experienced at least one grade 3 or 4 AE, most frequently thrombocytopenia or leukopenia (61.5% each). The overall response rate was 15.4%, disease control rate 69.2%, clinical benefit rate 23.1%, and two patients had a partial response (one in each dose group). Two patients treated with 250 mg QD had a progression-free survival > 6 months. PIM447 250 mg or 300 mg QD was tolerated in Japanese patients with R/R MM. Further studies are required to evaluate clinical outcomes of PIM447 in combination with other drugs for the treatment of MM.

Trial registration: clinicaltrials.gov: (NCT02160951).

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Acknowledgments

The study was supported by Novartis Pharmaceuticals Corporation. We thank the investigators of the study. We thank Kazuto Natsume (previously Novartis employee) who is currently working at AbbVie GK, Norifumi Ishikawa (previously Novartis employee) currently working at Nobelpharma Co., Ltd and K. Gary Vanasse (previously Novartis employee) for their significant contribution to this study. We also thank Bhavani Yamsani, M. Pharm, MBA, and Ambrin Fatima, PhD, of Novartis Healthcare Pvt. Ltd. for providing medical editorial and writing assistance with this manuscript.

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Authors and Affiliations

  1. Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, 1, Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Aichi, 467-8601, Japan

    Shinsuke Iida

  2. Department of Hematology, National Hospital Organization Okayama Medical Center, Okayama, Japan

    Kazutaka Sunami

  3. Division of Medical Oncology and Hematology, Kobe University Hospital, Kobe, Hyogo, Japan

    Hironobu Minami

  4. Department of Hematology and Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Koto-ku, Tokyo, Japan

    Kiyohiko Hatake

  5. Novartis Pharma K.K., Minato-ku, Tokyo, Japan

    Risa Sekiguchi, Kazuto Natsume & Norifumi Ishikawa

  6. Novartis Institutes for BioMedical Research, Cambridge, MA, USA

    Mikael Rinne

  7. Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan

    Masafumi Taniwaki

  8. Center for Molecular Diagnostics and Therapeutics, Kyoto Prefectural University of Medicine, Kyoto, Japan

    Masafumi Taniwaki

Authors
  1. Shinsuke Iida
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  2. Kazutaka Sunami
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  3. Hironobu Minami
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  4. Kiyohiko Hatake
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  5. Risa Sekiguchi
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  6. Kazuto Natsume
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  7. Norifumi Ishikawa
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  8. Mikael Rinne
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  9. Masafumi Taniwaki
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Correspondence to Shinsuke Iida.

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Iida, S., Sunami, K., Minami, H. et al. A phase I, dose-escalation study of oral PIM447 in Japanese patients with relapsed and/or refractory multiple myeloma. Int J Hematol 113, 797–806 (2021). https://doi.org/10.1007/s12185-021-03096-9

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  • DOI: https://doi.org/10.1007/s12185-021-03096-9

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