Journal Article

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

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

2025

Overview

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. Tasurgratinib (previously known as E7090) is a potent, selective FGFR1–3 inhibitor. The overall data from this first‐in‐human phase I study support a manageable safety profile and favorable preliminary antitumor activity of Tasurgratinib, particularly in patients with cholangiocarcinoma harboring FGFR2 gene rearrangements.

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc
• Subject: Adult / Aged / Alfacalcidol / Bile Duct Neoplasms - drug therapy / Bile Duct Neoplasms - genetics / Calcifediol / Cancer / Cancer patients / Care and treatment / Cell surface receptors / Cholangiocarcinoma / Cholangiocarcinoma - drug therapy / Cholangiocarcinoma - genetics / E7090 / Female / FGFR2 / Fibroblast growth factor receptor 1 / Fibroblast growth factor receptor 2 / Fibroblast growth factor receptors / Fibroblast Growth Factor-23 / Fibroblast growth factors / Fibroblasts / Gastric cancer / Gene amplification / Genetic aspects / Genomes / Growth factor receptors / Growth factors / Humans / Hyperphosphatemia / Kinases / Laboratories / Male / Medical records / Middle Aged / Mortality / Mutation / Oncology, Experimental / Original / ORIGINAL ARTICLE / Patients / Pharmacodynamics / Pharmacogenetics / Pharmacogenomics / Pharmacokinetics / Phosphates / Protein Kinase Inhibitors - administration & dosage / Protein Kinase Inhibitors - adverse effects / Protein Kinase Inhibitors - pharmacokinetics / Protein Kinase Inhibitors - therapeutic use / Pyrimidines - administration & dosage / Pyrimidines - adverse effects / Pyrimidines - pharmacokinetics / Pyrimidines - therapeutic use / Receptor, Fibroblast Growth Factor, Type 2 - antagonists & inhibitors / Receptor, Fibroblast Growth Factor, Type 2 - genetics / Receptors, Fibroblast Growth Factor - antagonists & inhibitors / Receptors, Fibroblast Growth Factor - genetics / Solid tumors / Stomach cancer / Stomach Neoplasms - drug therapy / Stomach Neoplasms - genetics / Stomach Neoplasms - pathology / Tasurgratinib / Tumors / Tyrosine / Vitamin D