Infigratinib demonstrated “promising” clinical activity in previously treated patients with advanced cholangiocarcinoma harboring FGFR2 fusions or rearrangements, researchers reported in The Lancet Gastroenterology and Hepatology.

The researchers conducted a phase 2 trial ( Identifier: NCT02150967) to evaluate the safety and efficacy of infigratinib, a selective ATP-competitive inhibitor of fibroblast growth factor receptors.

The study enrolled 108 patients with locally advanced or metastatic cholangiocarcinoma who had received 1 or more prior lines of therapy and had FGFR2 fusions or rearrangements.

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The patients’ median age was 53 years (range, 44-64 years), 62% were women, and 72% were White. One patient had stage II disease, and the rest had stage IV. Nearly half of patients (46%) had received 1 prior therapy, 30% had received 2, 13% had received 3, and 11% had received 4 or more prior therapies.

The patients received 125 mg of oral infigratinib once daily for 21 consecutive days on a 28-day cycle. Patients were treated until progression, intolerance, withdrawal, or death.

The median treatment duration was 5.5 months, and the median follow-up was 10.6 months.

The objective response rate, as assessed by blinded independent central review (BICR), was 23.1%. There were 24 partial responses and 1 confirmed complete response in a patient who had only non-target lesions identified at baseline.

The BICR-assessed objective response rate was numerically higher in patients who had 1 previous line of therapy (34%) compared with those who had 2 prior lines (15.6%), 3 prior lines (14.3%), or at least 4 prior lines (8.3%).

Overall, the median time to response was 3.6 months, and the median duration of response was 5.0 months. The disease control rate was 84.3%.

The median progression-free survival was 7.3 months, and the median overall survival was 12.2 months.

The most common treatment-related adverse events (AEs) of any grade were hyperphosphatemia (74%), stomatitis (51%), alopecia (32%), palmar-plantar erythrodysesthesia syndrome (32%), dry eye (31%), fatigue (29%), and arthralgia (29%).

Central serous retinopathy-like and retinal pigment epithelial detachment-like events were reported in 18 patients. Most of these AEs were grade 1 (n=10) or grade 2 (n=7), and 1 was grade 3.

AEs were mostly reversible and manageable, according to the researchers, and there were no treatment-related deaths.

“Infigratinib has promising clinical activity and a manageable adverse event profile in previously treated patients with locally advanced or metastatic cholangiocarcinoma harboring FGFR2 gene fusions or rearrangements, and so represents a potential new therapeutic option in this setting,” the researchers wrote.

Disclosures: This research was supported by QED Therapeutics and Novartis. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of 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 August 3, 2021. doi:10.1016/S2468-1253(21)00196-5