Phase I study of BGT226, a pan-PI3K and mTOR inhibitor, in Japanese patients with advanced solid cancers

  • Hironobu MinamiEmail author
  • Yutaka Fujiwara
  • Kei Muro
  • Masahiko Sato
  • Atsuko Moriya
Original Article


The phosphatidylinositol 3-kinase (PI3K) pathway is a promising therapeutic target for various cancers. BGT226 is a pan-PI3K and mammalian target of rapamycin (mTOR) inhibitor. The tolerability and pharmacokinetics/pharmacodynamics of BGT226 were investigated in a phase I study in Japanese patients with advanced solid cancers. BGT226 was orally administered on days 1, 3, and 5 of each week. The initial dose of 10 mg was subsequently escalated to 20, 40, 80, and 100 mg in a cohort of three patients. Pharmacokinetics and pharmacodynamics were investigated using plasma, normal skin, and tumor samples. A total of 18 patients were enrolled and evaluated. The most frequently reported toxicities were diarrhea, nausea, decreased appetite, vomiting, and fatigue. They were all grade 1 or 2, and no dose-limiting toxicity was observed. However, all six patients treated at 100 mg experienced diarrhea and nausea, while two experienced a dose reduction and/or interruptions during the study. Two of five patients who exhibited stable disease continued the study treatment for ≥ 16 weeks. The absorption of BGT226 was rapid, and systemic exposure increased in a dose-dependent manner. Treatment with BGT226 did not change any of the biomarkers in neither normal skin nor tumor tissues. BGT226 was tolerated up to 100 mg three times a week in Japanese patients with solid cancers, without difference in toxicity profiles and pharmacokinetics compared to Western patients.


PI3K mTOR Pharmacokinetics Pharmacodynamics BGT226 



This study was supported by Novartis Pharma K.K.

Compliance with ethical standards

Conflict of interest

Hironobu Minami has received research funding from Asahi-Kasei, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Eizai, Exelixis, Fuji, Kowa, Kyowa-Kirin, Lilly, Nihon Shinyaku, Novartis, Ono, Otsuka, Pfizer, Sanofi, Shire Japan, Taiho, and Takeda, and speaker honoraria from Bayer, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Eizai, Exelixis, Kowa, Kyowa-Kirin, Lilly, Novartis, Ono, Otsuka, Pfizer, Sanofi, Shire Japan, Taiho, and Takeda. Yutaka Fujiwara has received research funding from AbbVie, AstraZeneca, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Eisai, Eli Lilly, Incyte, Merck Serono, MSD, and Novartis, and speaker honoraria from Bristol-Myers Squibb, MSD, ONO, and Taiho.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Medical Oncology and HematologyKobe University Graduate School of MedicineKobeJapan
  2. 2.Cancer CenterKobe University HospitalKobeJapan
  3. 3.Department of Respiratory MedicineMitsui Memorial HospitalTokyoJapan
  4. 4.Department of Clinical Oncology and Outpatient Treatment CenterAichi Cancer Center HospitalNagoyaJapan
  5. 5.Novartis Pharma K.KTokyoJapan

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