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Clinical Trial
. 2025 Jan;116(1):192-203.
doi: 10.1111/cas.16354. Epub 2024 Oct 27.

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

Chigusa Morizane  1 , Makoto Ueno  2 , Tatsuya Ioka  3 , Masahiro Tajika  4 , Masafumi Ikeda  5 , Kensei Yamaguchi  6 , Hiroki Hara  7 , Hiroshi Yabusaki  8 , Atsushi Miyamoto  9 , Satoru Iwasa  1 , Manabu Muto  10 , Tsutomu Takashima  11 , Keiko Minashi  12 , Yoshito Komatsu  13 , Tomohiro Nishina  14 , Takako Eguchi Nakajima  15   16 , Atsuchi Takeno  17 , Toshikazu Moriwaki  18 , Masayuki Furukawa  19 , Takatoshi Sahara  20 , Hiroki Ikezawa  20 , Maiko Nomoto  20 , Shuya Takashima  20 , Taisuke Uehara  20 , Setsuo Funasaka  20 , Masakazu Yashiro  11 , Junji Furuse  2
Affiliations
Clinical Trial

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

Chigusa Morizane et al. Cancer Sci. 2025 Jan.

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)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.

Keywords: E7090; FGFR2; Tasurgratinib; cholangiocarcinoma; gastric cancer.

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Conflict of interest statement

C. Morizane received personal fees from Astra Zeneca, Taiho Pharmaceutical, and Nihon Servier and research funds from Eisai, Yakult, Ono Pharmaceutical, Taiho Pharmaceutical, J‐Pharma, AstraZeneca, Merck Biopharma, Daiichi Sankyo, and Boehringer Ingelheim. M. Ueno received personal fees from Taiho Pharmaceutical, AstraZeneca, K.K, Yakult Honsha, Nihon Servier, Incyte Biosciences Japan GK, and Chugai Pharmaceutical, and research funds from Taiho Pharmaceutical, AstraZeneca, MSD K.K, Nihon Servier, Ono Pharmaceutical, Incyte Biosciences Japan Company, Chugai Pharmaceutical, Boehringer Ingelheim GmbH, J‐Pharma, Eisai, Novartis Pharma K.K, Astellas Pharma Inc., DFP (Delta Fly Pharma), Novocure GmbH, and Chiome Bioscience. T. Ioka received personal fees from Taiho and Astra Zeneca. M. Ikeda received fees from AstraZeneca, Chugai Pharma, Eisai, Incyte, Lilly Japan, MSD, Novartis, Ono Pharmaceutical, Takeda, Teijin Pharma, Nihon Servier, Taiho Pharmaceutical; research funds from Astra Zeneca, Bayer, Bristol‐Myers Squibb, Chiome Bioscience, Chugai, Eisai, Eli Lilly Japan, Delta‐Fly Pharma, Invitae, J‐Pharma, Merck Biopharma, Merus N.V., MSD, Novartis, Nihon Servier, Ono Pharmaceutical, Syneos Health, and Rakuten Medical, and is an editorial board member of Cancer Science. T. Takashima received personal fees from Eisai. K. Minashi received research funds from Astellas, Taiho Pharma., Amgen, Daiichi‐Sankyo Pharma., MSD, and PPD‐SNBL K.K. Y. Komatsu received fees from Taiho Pharmaceutical, Daiichi Sankyo, MSD, Chugai Pharmaceutical, Ono Pharmaceutical, and Takeda Pharmaceutical, grants from Taiho Pharmaceutical, Chugai Pharmaceutical, and Nippon Kayaku, and research funds from National Cancer Center Japan and Aichi Cancer Center. T. Nishina received fees from Ono Pharmaceutical. T. Nakajima received research funds from KBBM and Takeda Pharmaceutical. M. Furukawa received researched funds from Merck Biopharma, MSD, Ono Pharma, J‐Pharma, Taiho Pharmaceutical, Incyte Japan, and Astellas Pharma. T. Sahara, H. Ikezawa, M. Nomoto, S. Takashima, T. Uehara, and S. Funasaka are all employees of Eisai. J. Furuse received fees from Ono Pharma, Chugai Pharma, Incyte Biosciences Japan, Fuji Film, Eisai, Eli Lilly, Astra Zeneca, and Yakult, grants from Eisai and Taiho Pharmaceutical, and research funds from MSD, J‐Pharma, and Delta‐Fly Pharma. M. Tajika, K. Yamaguchi, H. Hara, H. Yabusaki, A. Miyamoto, S. Iwasa, M. Muto, A. Takeno, T. Moriwaki, and M. Yashiro have no conflicts of interest to declare.

Figures

FIGURE 1
FIGURE 1
Efficacy of Tasurgratinib presented as (A) percentae change from baseline in the sum of diameter of the target lesion (dashed line represents a 30% reduction in tumor burden) and (B) a swimmer plot showing the duration of treatment, dosing history, and BOR. BOR, best overall response; PD, progressive disease; PR, partial response; SD, stable disease.
FIGURE 2
FIGURE 2
AUC correlation with (A) 1,25‐(OH)2‐vitamin D, (B) FGF23, and (C) serum phosphate. For 1,25‐(OH)2‐vitamin D (n = 30), Spearman correlation coefficients (R) = 0.61609, p = 0.0003. For FGF23 (n = 30), R = 0.62499, p = 0.0002. For serum phosphate (n = 32), R = 0.60931, p = 0.0002. AUC, area under the plasma concentration–time curve; FGF23, fibroblast growth factor 23.
FIGURE 3
FIGURE 3
Circulating tumor DNA genetic analysis for fusions in patient #1 (A), patient #5 (B), and patient #6 (C), and for FGFR2 mutations in patient #4 (D) and patient #5 (E). Baseline samples were collected within 4 days before cycle 1, day 1.
See this image and copyright information in PMC

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