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

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)<sub>2</sub>-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.

Authors

Institutions

Publication Details

Journal
Cancer Science
Published
2024-10-27
DOI
https://doi.org/10.1111/cas.16354
Citations
4
Primary Topic
Cholangiocarcinoma and Gallbladder Cancer Studies
Type
article
Field-Weighted Citation Impact
2.29

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

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

Chigusa Morizane, Atsushi Takeno, Atsushi Miyamoto, Takako Eguchi Nakajima et al.
4 citations
Cancer Science
Cholangiocarcinoma and Gallbladder Cancer Studies
2.29
article

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

Chigusa Morizane, Atsushi Takeno, Atsushi Miyamoto, Takako Eguchi Nakajima, Shuya Takashima, Taisuke Uehara, Masafumi Ikeda, Manabu Muto, Hiroshi Yabusaki, Tatsuya Ioka, Masahiro Tajika, Tsutomu Takashima, Hiroki Hara, Yoshito Komatsu, Keiko Minashi, Hiroki Ikezawa, Maiko Nomoto, Satoru Iwasa, Setsuo Funasaka, Tomohiro Nishina, Masakazu Yashiro, Kensei Yamaguchi, Toshikazu Moriwaki, Masayuki Furukawa, J. Furuse, Makoto Ueno, Takatoshi Sahara
article en
4 citations

Abstract

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)<sub>2</sub>-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.

Cancer ScienceVol. 116(1)
University of Tsukuba (JP), St. Marianna University School of Medicine (JP), Kyoto University (JP), Kanagawa Prefectural Hospital Organization (JP), Osaka National Hospital (JP), Niigata Cancer Center Hospital (JP), National Hospital Organization Kyushu Cancer Center (JP), Kansai Rosai Hospital (JP), University of Tsukuba Hospital (JP), Chiba Cancer Center (JP), Yamaguchi University Hospital (JP), Saitama Cancer Center (JP), Aichi Cancer Center (JP), The Cancer Institute Hospital (JP), Shikoku Cancer Center (JP), Hokkaido University Hospital (JP), National Cancer Center Hospital East (JP), Kyoto University Hospital (JP), Tokyo National Hospital (JP), Japanese Foundation For Cancer Research (JP), Kanagawa Cancer Center, Osaka Metropolitan University (JP), Eisai (Japan) (JP), Tokyo Metropolitan University (JP)
Eisai
Good health and well-being
Openalex Percentile: Top 11%
Cholangiocarcinoma and Gallbladder Cancer Studies
2.29
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.