Tasurgratinib (E7090) for cholangiocarcinoma with fibroblast growth factor receptor 2 fusions/rearrangements: a multicenter, open-label, Phase 2 study.

Background: This Phase 2 study (NCT04238715) evaluated the efficacy/safety of tasurgratinib 140 mg daily in patients with cholangiocarcinoma (CCA) and fibroblast growth factor receptor (FGFR) 2 fusions/rearrangements.

Methods: Eligible Japanese and Chinese patients who had surgically unresectable, advanced, or metastatic CCA and had received ≥1 prior gemcitabine-based combination chemotherapy regimen were included and treated with oral tasurgratinib 140 mg daily. The primary endpoint was objective response rate (ORR); the study was considered successful if the lower limit of the ORRs 90% CI was >15%. Secondary endpoints included duration of response and safety. FGFR2 fusions/rearrangements were confirmed by fluorescence in situ hybridization performed in central laboratories. Tumor responses were measured every 8 weeks by Response Evaluation Criteria in Solid Tumors version 1.1 per independent imaging review.

Results: Sixty-three patients were treated; 23 (37%) had received 1 prior regimen, all others had received ≥2. By the data cutoff date (15 March 2023), the ORR was 30.2% (two-sided 90% CI: 20.7-41.0). The median duration of response for responders was 5.6 months (95% CI: 3.7-9.3; range: 1.0+ to 14.8+). Sixty-one patients (97%) had ≥1 treatment-related treatment-emergent adverse event; 18 patients (29%) had ≥1 grade ≥3 treatment-related treatment-emergent adverse events. Four patients (6%) had a fatal adverse event, none were considered treatment-related. Tasurgratinib had promising antitumor activity in patients with CCA harboring FGFR2 fusions or rearrangements after ≥1 prior gemcitabine-based chemotherapy regimen.

Conclusions: The primary endpoint (ORR) met the study's predefined success criteria. Tasurgratinib had a manageable safety profile consistent with previous reports and the known pharmacological profile of FGFR inhibitors.