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

SATO, MASAHIKO and MORIYA, ATSUKO (2019) Phase I study of BGT226, a pan-PI3K and mTOR inhibitor, in Japanese patients with advanced solid cancers. Cancer Chemotherapy and Pharmacology, 84 (2). pp. 337-343. ISSN 14320843


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.

Item Type: Article
Keywords: BGT226 mTOR Pharmacodynamics Pharmacokinetics PI3K
Date Deposited: 25 Oct 2019 00:45
Last Modified: 25 Oct 2019 00:45