Gunagratinib in Patients with Previously Treated Advanced CCA Harboring FGFR2 Fusions or Rearrangements

March 2023, Vol 4, No 1 — April 4, 2023

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).

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 393070.

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.

Reference

  • Goyal L, Kongpetch S, Crolley VE, Bridgewater J. Targeting FGFR inhibition in cholangiocarcinoma. Cancer Treat Rev. 2021;95:102170.
  • 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.

    Related Items

    Characterization of Long-Term Survivors in TOPAZ-1
    March 2023, Vol 4, No 1
    Researchers examined the characteristics, outcomes, and genomic profiles of patients with advanced biliary tract cancer who were treated with durvalumab plus gemcitabine/cisplatin and experienced long-term survival.
    MDM2-p53 Antagonist BI 907828 Demonstrated Promising Activity in Patients with Advanced BTC
    March 2023, Vol 4, No 1
    The novel MDM2-p53 antagonist BI 907828 is being investigated as a first-line treatment in patients with advanced biliary tract cancer.
    Treatment and Survival Outcomes with Systemic Therapy for Patients with BTC with IDH1 Mutations: A Retrospective Study
    March 2023, Vol 4, No 1
    Long-term outcomes were evaluated in patients with IDH1-mutated biliary tract cancer who were treated with systemic therapy.
    Phase 2 Study of CTX-009 plus Paclitaxel in Patients with Advanced BTC
    March 2023, Vol 4, No 1
    CTX-009 plus paclitaxel showed promising efficacy as second- or third-line treatment in patients with advanced biliary tract cancer.
    Results from SWOG 1815: GemCis and Nab-Paclitaxel versus GemCis in Advanced BTC
    March 2023, Vol 4, No 1
    The SWOG 1815 trial found that treatment with gemcitabine/cisplatin and paclitaxel (GAP) did not result in a significant improvement in survival compared with gemcitabine and cisplatin in patients with advanced biliary tract cancer, though GAP may be beneficial in patients with locally advanced disease and GBC.
    JCOG1202 Subgroup Analysis: Risk Factors for Early Relapse in Patients Undergoing Curative Resection
    March 2023, Vol 4, No 1
    A study of patients with resected biliary tract cancer (BTC) found that postoperative CA 19-9 level, tumor differentiation, lymph node metastases, and residual tumor significantly impact early relapse in patients with curatively resected BTC. Similar risk factors were also found in patients receiving adjuvant S-1.
    Impact of Gene Expression in 5-FU Metabolic Pathways on Outcomes in Patients Enrolled in JCOG1202
    March 2023, Vol 4, No 1
    Results from a study evaluating the impact of 5-FU metabolic pathway enzyme expression on outcomes of patients with curatively resected biliary tract cancer showed that relapse-free survival was improved in patients with certain enzymes who received adjuvant S-1.
    Atezolizumab with or without Bevacizumab in Combination with GemCis in Advanced BTC: Results from IMbrave 151
    March 2023, Vol 4, No 1
    Researchers assessed whether VEGF blockade plus chemotherapy with gemcitabine/cisplatin can enhance responses to PD-L1 inhibition by promoting an immune-permissive tumor microenvironment in patients with advanced biliary tract cancer.
    Nab-Paclitaxel plus Sintilimab as Second-Line Treatment for Advanced BTC
    March 2023, Vol 4, No 1
    The safety and efficacy of second-line nab-paclitaxel combined with the anti-PD-1 antibody sintilimab was studied in patients with advanced biliary tract cancer.
    ICIs as Salvage Therapy for BTCs with KRAS Mutation
    March 2023, Vol 4, No 1
    Results are presented from a retrospective analysis of molecular profiles in patients with biliary tract cancers to assess the efficacy of immune checkpoint inhibitors according to KRAS mutation.

    Subscribe Today!

    To sign up for our newsletter or print publications, please enter your contact information below.

    I'd like to receive: