Efficacy and Safety of Infigratinib in Patients with Previously Treated Advanced CCA with an FGFR2 Gene Fusion or Rearrangement

Web Exclusives — December 20, 2021

Infigratinib is a selective ATP-competitive oral tyrosine kinase inhibitor of FGFR1-3 that is approved for use in patients with advanced cholangiocarcinoma (CCA) who harbor FGFR2 alterations. The approval was based on the results of a single-arm, multicenter, open-label, phase 2 study (ClinicalTrials.gov Identifier: NCT02150967) that evaluated the efficacy and safety of infigratinib in patients with previously treated advanced CCA who harbor FGFR2 fusions. The final results of this study were published in The Lancet Gastroenterology Hepatology.

Eligibility criteria included patients aged ≥18 years with histologically or cytologically confirmed advanced or metastatic CCA who harbored FGFR2 fusions or other FGFR alterations and whose disease had progressed on or who were intolerant to ≥1 prior cisplatin- or gemcitabine-based therapies. Eligible patients, who were recruited from 18 academic centers and hospitals, received oral infigratinib 125 mg once daily on days 1 to 21 every 28 days, until unacceptable toxicity, disease progression, withdrawal of consent, or death. The primary end point was objective response rate (ORR), as assessed by blinded independent central review (BICR) according to RECIST version 1.1 with duration of response. Secondary end points included progression-free survival (PFS), disease control rate, overall survival (OS), safety, and tolerability. Radiologic tumor evaluation was performed at baseline and every 8 weeks until disease progression. The primary outcome and safety were analyzed in the full analysis set (FAS), which comprised all patients who received ≥1 doses of infigratinib.

At data cutoff (June 23, 2014, to March 31, 2020), a total of 122 patients were enrolled in the study. The FAS included 108 patients with FGFR2 fusions or rearrangements who received ≥1 doses of infigratinib. The median age of the study population was 53 years, 94% had extrahepatic metastatic disease, 54% had received ≥2 prior treatment lines, and 81% had FGFR2 fusions.

After a median follow-up of 10.6 months, 96 (88.9%) patients discontinued treatment. In the FAS, BCIR-assessed ORR was 23.1% (95% confidence interval [CI], 15.6-32.2), with 1 confirmed complete response (the patient had nontarget lesions only at baseline) and 24 partial responses. The median time to response was 3.6 months, the median duration of response was 5.0 months, and the disease control rate was 84.3%. ORRs were comparable in subgroups tested by age, lines of previous treatment, gender, baseline Eastern Cooperative Oncology Group performance status, disease stage, and geographic region. The median PFS was 7.3 months (95% CI, 5.6-7.6) and the median OS was 12.2 months (95% CI, 10.7-14.9).

Per safety analysis, the most common treatment-emergent adverse events (any grade) were hyperphosphatemia (n = 83), stomatitis (n = 59), fatigue (n = 43), and alopecia (n = 41); no treatment-related deaths were reported. Ocular toxicity included dry eyes (n = 37) and central serous retinopathy-like and retinal pigment epithelial detachment─like events (n = 18), of which 1 event was grade 3.

Based on these results, the authors concluded that infigratinib demonstrates promising antitumor activity and a manageable adverse event profile in previously treated patients with locally advanced or metastatic CCA who harbor FGFR2 gene fusions or rearrangements, thus representing a new therapeutic option in this setting.

On May 28, 2021, the US Food and Drug Administration (FDA) granted accelerated approval to infigratinib for adults with previously treated, unresectable locally advanced or metastatic CCA with an FGFR2 fusion or other rearrangement, as detected by an FDA-approved test. The FDA also approved FoundationOne® CDx for selection of patients with FGFR2 fusion or other rearrangement, as a companion diagnostic device for treatment with infigratinib.


Javle M, Roychowdhury S, Kelley RK, et al. Infigratinib (BGJ398) in previously treated patients with advanced or metastatic cholangiocarcinoma with FGFR2 fusions or rearrangements: mature results from a multicentre, open-label, single-arm, phase 2 study. Lancet Gastroenterol Hepatol. 2021;6:803-815.

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