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The FGFR-selective tyrosine kinase inhibitor infigratinib shows promising efficacy in patients advanced cholangiocarcinoma harbouring FGFR2 alterations

Patients with advanced cholangiocarcinoma (CCA) progressing after their first-line gemcitabine-based therapy have very limited treatment options. To address this medical need, a phase II trial evaluated the potential of the FGFR1-3-selective oral tyrosine kinase inhibitor infigratinib in previously treated advanced CCA patients harbouring a FGFR2 gene fusion, or rearrangement. Final results of this trial, presented at ASCO GI 2021, indicate an objective response to this agent in a quarter of patients, resulting in a median progression-free survival (PFS) of 7.3 months.


CCA is a rare and aggressive malignancy, with a relative 5-year survival of only 2% for patients with distant CCA at diagnosis. The majority of patients with CCA is diagnosed with late-stage disease and are faced with limited treatment options. The current standard of care in first line consists of a chemotherapy doublet of gemcitabine and cisplatin. For patients progressing on this first line therapy, very few effective therapies are available. Recently, increasing insights into the molecular drivers underlying the CCA pathogenesis have opened to door towards better, personalized treatment options. In this respect, FGFR fusions are seen in approximately 15% of intrahepatic CCA cases and represent an interesting therapeutic target. Following promising (pre)clinical signals, the FGFR1-3-selective oral tyrosine kinase inhibitor infigratinib was evaluated in a phase II including patients with previously treated advanced CCA harbouring FGFR fusions or rearrangements. In the 1st cohort of this study, 108 participants with FGFR2 alterations, who did not receive a prior FGFR inhibitor, received infigratinib 125mg orally for 21 days of each 28-day cycle until unacceptable toxicity or disease progression. All patients also received phosphate-binding prophylaxis with sevelamer.

Infigratinib induces an overall response rate of 23%

The median age of patients in the study was 53 years and they received a median of 2 prior lines of therapy (range 0-8). At a median follow-up of 10.6 months, an overall response rate (ORR) of 23.1% was reported, including one complete and 24 partial responses. The disease control rate with infigratinib was 84.3%. Responses to infigratinib happened fast with a median time to response of 3.6 months and proved to be durable with a median response duration of 5.0 months. Interestingly, a third of the responders had a treatment response lasting for at least 6 months. The median progression-free survival (PFS) for patients in the study was 7.3 months, with a 4-month PFS rate of 75%. The median OS in the study reached 12.2 months. Among patients receiving infigratinib in 2nd-line setting, an ORR of 34% was reported, which is markedly higher than the 13.8% ORR seen in patients treated in 3rd line or beyond.

The most common any-grade treatment-emergent adverse events consisted of hyperphosphataemia (76.9%), eye disorders (67.6%, excluding retinopathy/retinal pigment epithelium detachment [CSR/RPED]), stomatitis (54.6%) and fatigue (39.8%). Overall, 16.7% of patients experienced CSR/RPED. Grade 3/4 TEAEs included stomatitis (14.8%), hyponatraemia (13.0%) and hypophosphataemia (13.0%).


The results of this phase II trial demonstrate important anticancer activity of infigratinib in patients with advanced CCA and FGFR2 alterations. These promising efficacy data in combination with the manageable safety profile of this drug form the basis for a phase III trial comparing infigratinib to gemcitabine/cisplatin as a frontline therapy for advanced CCA patients.


Javle M et al., Final results from a phase II study of infigratinib (BGJ398), an FGFR-selective tyrosine inhibitor, in patients with previously treated advanced cholagiocarcinoma harbouring an FGFR2 gene fusion or rearrangement. Presented at ASCO GI 2021; Abstract 265.

Speaker Milind Javle

Milind Javle

Milind Javle, MD, MD Anderson Cancer Center, Houston, Texas, USA


See: Keyslides

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