Background: ICP-192 (gunagratinib), developed by InnoCare Pharma, is a novel pan-FGFR (fibroblast growth factor receptors) inhibitor that potently and selectively inhibits FGFR 1, 2, 3 and 4 activities irreversibly by covalent binding. Here we present data from an ongoing phase IIa dose-expansion study (ICP-CL-00301 NCT03758664) of gunagratinib in patients with cholangiocarcinoma (CCA). Methods: Eligible participants were aged 18-75 years, had locally advanced or metastatic CCA with FGFR2 fusions or rearrangements, and had disease progression after ≥1 prior treatment or intolerant of prior treatment. Patients received oral gunagratinib 20 mg QD (21-day cycle) until disease progression, intolerance, withdrawal of consent, or death. Radiological tumor evaluation was done at baseline and every 6 weeks until disease progression. Primary endpoint was objective response rate (ORR). Results: As of September 5, 2022, 18 CCA patients were enrolled and received 20 mg gunagratinib. The median age of the patients was 52.0 with 44.4% male and ECOG between 0-2. Median follow-up was 5.57 months. Among the 17 patients who have completed at least one tumor assessment, 9 patients had confirmed partial response (PR) and 7 patients had stable disease (SD). The ORR was 52.9% (9/17). The disease control rate (DCR) was 94.1% (16/17). The median progression free survival (mPFS) was 6.93 months (95% CI, 5.42–not reached) (not mature at cutoff). Among the 17 patients with safety data, 16 (94.1%) patients experienced at least one treatment-emergent adverse event (TEAE). Grade 3 or higher TEAEs occurred in 35.3% of patients. Five serious TEAE were reported with only one serious treatment-related adverse event (TRAE). Discontinuation rate due to TRAEs was 0%. There were no treatment-related deaths. Conclusions: The study data demonstrated that gunagratinib is safe and well-tolerated in previously treated patients with locally advanced or metastatic CCA harboring FGFR2 gene fusions or rearrangements. The response rate in such a patient group is high comparing to other approved FGFR inhibitors. Gunagratinib is a promising second-generation FGFR inhibitor with potential for the treatment of multiple indications with FGF/FGFR pathway abnormalities. Clinical trial information: NCT03758664.

Data cut-off date: 2022-09-05. * One patient missed the first tumor assessment because of COVID-19 and was PD at the second tumor assessment.