Tasurgratinib in patients with cholangiocarcinoma or gastric cancer: Expansion part of the first-in-human phase I study.

Autor: Morizane C; National Cancer Center Hospital, Tokyo, Japan., Ueno M; Kanagawa Cancer Center, Yokohama, Japan., Ioka T; Oncology Center, Yamaguchi University Hospital, Ube, Japan., Tajika M; Aichi Cancer Center Hospital, Nagoya, Japan., Ikeda M; National Cancer Center Hospital East, Kashiwa, Japan., Yamaguchi K; The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan., Hara H; Saitama Cancer Center, Saitama, Japan., Yabusaki H; Niigata Cancer Center Hospital, Niigata, Japan., Miyamoto A; National Hospital Organization Osaka National Hospital, Osaka, Japan., Iwasa S; National Cancer Center Hospital, Tokyo, Japan., Muto M; Kyoto University Hospital, Kyoto, Japan., Takashima T; Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan., Minashi K; Chiba Cancer Center, Chiba, Japan., Komatsu Y; Hokkaido University Hospital, Sapporo, Japan., Nishina T; National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan., Nakajima TE; St. Marianna University School of Medicine, Kawasaki, Japan.; Department of Early Clinical Development, Kyoto University Graduate School of Medicine, Kyoto, Japan., Takeno A; Kansai Rosai Hospital, Amagasaki, Japan., Moriwaki T; University of Tsukuba Hospital, Tsukuba, Japan., Furukawa M; National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan., Sahara T; Eisai Co., Ltd., Tokyo, Japan., Ikezawa H; Eisai Co., Ltd., Tokyo, Japan., Nomoto M; Eisai Co., Ltd., Tokyo, Japan., Takashima S; Eisai Co., Ltd., Tokyo, Japan., Uehara T; Eisai Co., Ltd., Tokyo, Japan., Funasaka S; Eisai Co., Ltd., Tokyo, Japan., Yashiro M; Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan., Furuse J; Kanagawa Cancer Center, Yokohama, Japan.
Jazyk: angličtina
Zdroj: Cancer science [Cancer Sci] 2024 Oct 27. Date of Electronic Publication: 2024 Oct 27.
DOI: 10.1111/cas.16354
Abstrakt: Fibroblast growth factor receptors (FGFRs) are a highly conserved family of transmembrane receptor tyrosine kinases with multiple roles in the regulation of key cellular processes. Specific FGFR mutations have been observed in several types of cancers, including gastric carcinoma and cholangiocarcinoma. Dose escalation data of 24 Japanese patients with solid tumors treated with Tasurgratinib (previously known as E7090), a potent, selective FGFR1-3 inhibitor, was reported in a phase I, first-in-human, single-center study. Based on the safety, pharmacokinetic, and pharmacodynamic profiles observed in this study, the recommended dose of 140 mg once daily was selected for the expansion part (Part 2), a multicenter expansion of the dose-finding study restricted to patients with tumors harboring FGFR gene alterations. Safety and preliminary efficacy were assessed in Part 2. Pharmacodynamic pharmacogenomic markers (serum phosphate, FGF23, and 1,25-(OH) 2 -vitamin D, circulating tumor DNA) and pharmacokinetic profiles were also evaluated. A total of 16 patients were enrolled in Part 2, six with cholangiocarcinoma and 10 with gastric cancer. The most common treatment-emergent adverse events were hyperphosphatemia, palmar-plantar erythrodysesthesia syndrome, and paronychia. Five partial responses (83.3%) in cholangiocarcinoma patients and one partial response (11.1%) in gastric cancer patients were observed; median progression-free survival was 8.26 months (95% confidence interval [CI] 3.84, not evaluable [NE]) and 3.25 months (95% CI 0.95, 4.86), and overall survival was 22.49 months (95% CI 6.37, NE) and 4.27 months (95% CI 2.23, 7.95), respectively, in the two groups. In conclusion, Tasurgratinib 140 mg has a tolerable safety profile with good clinical efficacy in patients with cholangiocarcinoma harboring FGFR2 gene rearrangements.
(© 2024 The Author(s). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)
Databáze: MEDLINE
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