The Use of Gunagratinib in Patients With Previously Treated Advanced CCA Harboring FGFR2 Fusions or Rearrangements: A Phase 2 Study

Gunagratinib is being investigated in an ongoing phase 2a dose-expansion study in patients with cholangiocarcinoma.

Approximately 10% to 15% of patients with cholangiocarcinoma (CCA) have FGFR fusions or rearrangements, mostly affecting those with intrahepatic cancers. FGFR inhibitors have demonstrated promising results in clinical trials with patients harboring these mutations. Gunagratinib (ICP-192), a novel pan-FGFR inhibitor, irreversibly and selectively inhibits FGFR1, -2, -3, and -4. At ASCO Gastrointestinal Cancers Symposium 2023, Ye Guo, MD, 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).

At ASCO Gastrointestinal Cancers Symposium 2023, Ye Guo, MD, presented results from an ongoing phase 2a dose-expansion study of gunagratinib in patients with CCA.

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). In all, 9 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 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.

Gunagratinib is well tolerated by patients with CCA with FGFR2 gene fusions who have previously received treatment. Response rates indicate that gunagratinib, a second-generation FGFR inhibitor, is effective and has the potential to treat a variety of 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.