FGFR fusions or rearrangements occur in about 10% to 15% of patients with cholangiocarcinoma (CCA), mostly affecting patients with intrahepatic CCA.1 Clinical trials have demonstrated promising results with FGFR inhibitors in patients harboring these mutations with the hope of improving clinical outcomes. Gunagratinib (ICP-192) is a novel pan-FGFR inhibitor that irreversibly and selectively inhibits FGFR1, -2, -3, and -4. Dr Ye Guo presented results from an ongoing phase 2a dose-expansion study of gunagratinib in patients with CCA.
Participants were aged 18 to 75 years with locally advanced or metastatic CCA with FGFR2 fusions or rearrangements. Eligible patients had disease progression after ≥1 prior treatment or were intolerant of prior treatment. A total of 18 patients with CCA were enrolled and received 20 mg of gunagratinib daily until disease progression, intolerance, withdrawal from trial, or death. The primary end point was objective response rate (ORR).
After a median follow-up of 5.57 months, 17 patients completed ≥1 tumor assessment. The ORR was 52.9%, and the disease control rate was 94.1%. The median progression-free survival was 6.93 months (95% confidence interval, 5.42-not reached). Nine patients had a confirmed partial response, and 7 patients had stable disease (Table).
Of the 17 patients, 94.1% experienced ≥1 treatment-emergent adverse event (TEAE). Grade 3 or higher TEAEs occurred in 35.3% of patients, with the most common being increases in aspartate/alanine aminotransferase, nail disorders, and anemia. No discontinuations occurred due to TEAEs, and only 1 serious treatment-related adverse event and no treatment-related deaths occurred.
These results demonstrate that gunagratinib is well tolerated in patients with CCA with FGFR2 gene fusions who have received prior treatment. Response rates show promising efficacy of gunagratinib as a second-generation FGFR inhibitor and demonstrate its potential to treat multiple FGFR pathway abnormalities.
Source: Guo Y, Yuan C, Ding W, et al. Gunagratinib, a highly selective irreversible FGFR inhibitor, in patients with previously treated locally advanced or metastatic cholangiocarcinoma harboring FGFR2 fusions or rearrangements: a phase IIa dose-expansion study. Poster presented at: ASCO Gastrointestinal Cancers Symposium, January 19-21, 2023; San Francisco, CA. Abstract 572.
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