Infigratinib Shows Meaningful Clinical Activity for Chemotherapy-Refractory Cholangiocarcinoma With FGFR2 Fusions or Rearrangements

Investigators evaluated the antitumor activity of infigratinib in patients with previously treated, locally advanced or metastatic cholangiocarcinoma and FGFR2 alterations.

Infigratinib demonstrated meaningful clinical activity in patients with previously treated cholangiocarcinoma and fibroblast growth factor receptor-2 (FGFR2) fusions or rearrangements, investigators reported in Lancet Gastroenterology and Hepatology.

The multicenter, open-label, single-arm, phase 2 study evaluated the antitumor activity of infigratinib in patients with locally advanced or metastatic cholangiocarcinoma, FGFR2 alterations, and previous gemcitabine-based treatment. Patients were recruited from 18 academic centers and hospitals in the United States, Belgium, Spain, Germany, Singapore, Taiwan, and Thailand.

In this first cohort of the ongoing trial, participants were treated with 125 mg of oral infigratinib once daily, for 21 consecutive days of 28-day cycles, which continued until disease progression, intolerance, withdrawal of consent, or death. The study investigators evaluated radiologic tumors at baseline and every 8 weeks until disease progression via computed tomography or magnetic resonance imaging of the chest, abdomen, and pelvis.

Objective response rate was the primary endpoint. It was defined as the proportion of patients with a best overall response of a confirmed complete or partial response, assessed by blinded independent central review (BICR) according to Response Evaluation Criteria in Solid Tumors, version 1.1.

From June 23, 2014, to March 31, 2020, 122 patients were enrolled. Of this group, 108 patients with FGFR2 fusions or rearrangements were included in cohort 1, received at least 1 dose of infigratinib, and comprised the full analysis set. Participants’ median age was 53 years, 62% were women, and 72% were White.

The BICR-assessed objective response rate was 23.1% (95% CI, 15.6-32.2; 25 of 108 patients) after a median follow-up of 10.6 months (interquartile range [IQR], 6.2-15.6 months). There was 1 confirmed complete response observed in a patient who only had nontarget lesions identified at baseline, along with 24 partial responses. Additionally, 88 (88%) of 100 patients who had postbaseline measurements of target lesions had reduced BICR-assessed tumor burden.

The study cohort had a median time to response of 3.6 months (IQR, 1.8-3.8 months), a median duration of response of 5.0 months (IQR, 3.7-9.3 months), and a disease control rate of 84.3% (95% CI, 76.0-90.6). The investigator-assessed objective response rate was 30.6% (95% CI, 22.1%-40.2%; 33 of 108 patients), and the median investigator-assessed duration of response was 6.0 months (IQR, 4.9-9.2 months).

Among treatment-emergent adverse events (TEAEs) of any grade, the most frequently occurring were hyperphosphatemia (n=83), stomatitis (n=59), fatigue (n=43), and alopecia (n=41). Grade 3 TEAEs were observed in 61 (56%) patients, and grade 4 TEAEs occurred in 9 (8%) patients. A total of 34 (31%) patients had a serious adverse event, with anemia (n=4), pyrexia (n=4), hypercalcemia (n=3), and sepsis (n=3) being the most common.

The investigators noted that the single-arm, open-label study design may be a limitation, but it was considered appropriate due to the lack of available treatments in this setting.

“Infigratinib, administered as a second-line or later-line treatment, represents a potential new therapeutic option for patients with cholangiocarcinoma and FGFR2 fusions or rearrangements,” stated the researchers. “Results from cohorts 2 and 3 of this study will provide further clarification regarding the role of infigratinib in patients with cholangiocarcinoma and FGFR1 and FGFR3 fusions and rearrangements, FGFR1, FGFR2, and FGFR3 mutations, and in patients previously treated with FGFR inhibitors other than infigratinib,” they concluded.

Disclosure: This study was funded by Novartis and QED Therapeutics, an affiliate of BridgeBio. Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


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. Published online August 3, 2021. doi: 10.1016/S2468-1253(21)00196-5.