Phase I study of duvelisib in Japanese patients with relapsed or refractory lymphoma

Abstract

Duvelisib is a novel dual inhibitor of phosphoinositide-3-kinase (PI3K)-δ and -γ. This single-arm, multicenter phase I study investigated its safety, pharmacokinetics, and preliminary efficacy in Japanese patients with relapsed or refractory lymphoma. Duvelisib was administered orally twice daily at 25 mg in 28-day cycles. Seven patients, comprising 4 with follicular lymphoma (FL), 2 with diffuse large B-cell lymphoma, and 1 with mantle cell lymphoma (MCL) were enrolled. No dose-limiting toxicity occurred in any patient. The most commonly experienced treatment-related adverse events of any grade were neutropenia and thrombocytopenia, occurring in 3 patients each (42.9%); followed by lymphopenia, diarrhea, enterocolitis, stomatitis, hepatic function abnormal, ALT increased, and AST increased, occurring in 2 patients each (28.6%). The most common grade ≥ 3 treatment-related adverse events were neutropenia, which occurred in 3 patients (42.9%), and thrombocytopenia, lymphopenia, and hepatic function abnormal, which occurred in 2 patients each (28.6%). One patient with FL achieved a complete response; the remaining 3 with FL and the 1 with MCL achieved a partial response. The overall response rate was 71.4% (5/7 patients). Duvelisib was well tolerated in Japanese patients with relapsed or refractory lymphoma. Safety and preliminary efficacy data support further development of duvelisib in Japanese patients.

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Acknowledgements

This work was funded by AbbVie GK, and supported by Verastem Oncology and Infinity Pharmaceuticals. We would like to thank all of the patients, investigators, and support staff who participated in this phase I study. Verastem Inc. provided biostatistical programming support. Yakult Honsha Co., Ltd. and Verastem, Inc. provided medical writing and editorial assistance.

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Correspondence to Koji Izutsu.

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KI reports grants from Abbvie during the conduct of the study; grants and personal fees from Abbvie, Gilead Sciences, Eisai, MSD, Takeda, Janssen, Mundipharma, Chugai, AstraZeneca, Bayer, Ono, Celgene, and Kyowa Kirin outside the submitted work; and personal fees from Bristol Myers Squib, Dainihon Sumitomo, Nihon Mediphysics; grants from Zenyaku, Solasia, Symbio, Astellas, Astellas Amgen, and Daiichi Sankyo outside the submitted work. KK reports grants from AbbVie during the conduct of the study; grants and personal fees from AbbVie, Celgene, Chugai, Eisai, Janssen, Novartis, Takeda, Kyowa-Kirin, and Ono outside the submitted work; and personal fees from AstraZeneca, MSD, Mundi, and Dainippon-Sumitomo outside the submitted work. HK reports grants and personal fees from Daiichi Sankyo, Astellas, and Novartis Pharma outside the submitted work; grants from Chugai Pharmaceutical, Kyowa Kirin, Zenyaku Kogyo, FUJIFILM, Otsuka Pharmaceutical, Takeda Pharmaceutical, Sumitomo Dainippon Pharma, Sanofi, Celgene, Nippon Shinyaku, Eisai, and Pfizer Japan outside the submitted word; and personal fees from Bristol-Myers Squibb, and Amgen Astellas BioPharma outside the submitted work. GY has nothing to disclose. KS reports grants and personal fees from Eisai, Celgene, Chugai Pharmaceutical, Kyowa Kirin, and Daiichi Sankyo outside the submitted work; personal fees from AstraZeneca, Takeda Pharmaceutical, Janssen Pharmaceutical, Bristol-Myers Squibb, and Nippon Shinyaku outside the submitted work; and grants from Otsuka Pharmaceutical, and MSD outside the submitted work. KA reports grants and personal fees from Eisai, Takeda, Janssen, Bristol-Myers Squib, Chugai, Astellas, Daiichi Sankyo, Kyowa Kirin, and Otsuka Pharmaceutical outside the submitted work; personal fees from Abbvie, Celgene, Astellas Amgen, and Novartis outside the submitted work; and grants from Dainihon Sumitomo, Ono, Asahi Kasei Pharma, Shionogi, Yakult, Taiho, Mochida, Japan Blood Products, Nihon Kayaku, Shin Nippon Biomedical, Fujifilm Toyama Chemical, Nippon Shinyaku, Nihon Pharmaceutical, Sanofi, and Otsuka Pharmaceutical Factory outside the submitted work.

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Izutsu, K., Kato, K., Kiyoi, H. et al. Phase I study of duvelisib in Japanese patients with relapsed or refractory lymphoma. Int J Hematol (2020). https://doi.org/10.1007/s12185-020-02929-3

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Keywords

  • Clinical trial
  • PI3K
  • Japanese
  • Lymphoma
  • Duvelisib