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A multicenter phase I study of inebilizumab, a humanized anti-CD19 monoclonal antibody, in Japanese patients with relapsed or refractory B-cell lymphoma and multiple myeloma

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Abstract

This multicenter, phase I, open-label dose escalation study evaluated safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity of inebilizumab in Japanese patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), or multiple myeloma (MM) who were ineligible for hematopoietic stem cell transplantation. Patients received inebilizumab 2, 4, or 8 mg/kg intravenously on days 1 and 8 of the first 28-day cycle, and once every 28 days thereafter, with a 12 mg/kg cohort added. Twenty patients (11 FL, six DLBCL, two CLL, and one MM) received inebilizumab at four dose levels (2 mg/kg cohort, n = 3; 4 mg/kg cohort, n = 7; 8 mg/kg cohort, n = 4; 12 mg/kg cohort, n = 6). Three patients experienced dose-limiting toxicities: grade 4 neutropenia/grade 3 leukopenia (n = 1, 12 mg/kg) and grade 3 infusion reaction (n = 1 each, 4 mg/kg and 12 mg/kg); the maximum tolerated dose was 8 mg/kg. Four (three FL and one DLBCL) patients achieved complete response; eight (six FL and two DLBCL) achieved partial response. Overall response rate was 60%. Over the dose ranges evaluated, the pharmacokinetic profile of inebilizumab in Japanese patients was generally dose proportional. This phase I study showed acceptable toxicity and preliminary and promising efficacy of inebilizumab in patients with relapsed/refractory FL and DLBCL.

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Acknowledgements

The authors thank the patients who participated in this study and their families. We also thank all the investigators, nursing staff, and research support staff who contributed to the study. Medical writing and editorial support were provided by Amy Zannikos, PharmD, of Peloton Advantage (Parsippany, NJ) and funded by MedImmune, the global biologics R&D arm of AstraZeneca.

Author information

Author notes

  1. Koichi Fukino

    Present address: Clinical Development, Allergan Japan K.K., Tokyo, Japan

  2. Ken Ohmachi and Michinori Ogura contributed equally to this work.

Authors and Affiliations

  1. Department of Hematology and Oncology, Tokai University Hospital, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1143, Japan

    Ken Ohmachi, Kiyoshi Ando & Yoshiaki Ogawa

  2. Kasugai Municipal Hospital, Kasugai, Japan

    Michinori Ogura

  3. Department of Hematology and Oncology, Japanese Red Cross Nagoya Daini Hospital, Nagoya, Japan

    Michinori Ogura, Toshiki Uchida & Miki Kobayashi

  4. Department of Hematology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan

    Youko Suehiro, Ilseung Choi & Jun Okamura

  5. AstraZeneca K.K., Osaka, Japan

    Koichi Fukino & Yuki Yokoi

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  1. Ken Ohmachi
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Corresponding author

Correspondence to Ken Ohmachi.

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Conflict of interest

K.O., M.O., Y.S., K.A., T.U., I.C., Y.O., M.K. and J.O. have received research Grants from AstraZeneca. K.F. was an employee of AstraZeneca and owned stock/stock options in the company at the time of the study. Y.Y. is an employee of AstraZeneca and owns stock/stock options in the company. This study was designed under the responsibility of MedImmune, the global biologics R&D arm of AstraZeneca, the study was funded by MedImmune, and the study drug was provided by MedImmune. Each author had full access to the data, made substantial contributions to the drafting and/or revision of this manuscript, and granted approval for the submission of this paper. No author received an honorarium or other form of financial support related to the development of this manuscript.

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Ohmachi, K., Ogura, M., Suehiro, Y. et al. A multicenter phase I study of inebilizumab, a humanized anti-CD19 monoclonal antibody, in Japanese patients with relapsed or refractory B-cell lymphoma and multiple myeloma. Int J Hematol 109, 657–664 (2019). https://doi.org/10.1007/s12185-019-02635-9

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  • DOI: https://doi.org/10.1007/s12185-019-02635-9

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