FDA Grants Accelerated Approval of Infigratinib for FGFR2+ Cholangiocarcinoma

The FDA has granted accelerated approval to the oral FGFR1-3 selective inhibitor, infigratinib for the treatment of patients with cholangiocarcinoma who harbor an FGFR2 gene fusion or rearrangement.

The FDA has granted accelerated approval to the oral FGFR1-3 selective inhibitor, infigratinib (Truseltiq) for the treatment of patients with cholangiocarcinoma who harbor an FGFR2 gene fusion or rearrangement, announced BridgeBio Pharma, Inc, with QED Therapeutics, Inc., and Helsinn Group, in a press release.1

“While targeted treatments have extended survival for many types of cancer, people diagnosed with cholangiocarcinoma have previously been presented with extremely limited treatment options coupled with low statistical survival data,” said Milind M. Javle, MD, professor, Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, in a statement “In this study, Truseltiq showed promise as a targeted treatment option for patients with FGFR2-fusion-driven cholangiocarcinoma with a well-tolerated safety profile in line with previous observations in this patient population.”

Results from a phase 2, multicenter, single-arm study (NCT02150967) of infigratinib as third- or later-line treatment of patients with FGFR2 fusion-positive cholangiocarcinoma served as the basis for the New Drug Application. In the study, anticancer activity was observed with infigratinib and the agent also displayed a manageable safety profile, according to final results from the study presented during the American Society of Clinical Oncology Gastrointestinal Cancers Symposium (ASCO GU).2

A total of 107 patients with advanced/metastatic cholangiocarcinoma who progressed on 23 or more prior systemic therapies were enrolled in the study. The population had a median age of 53 years (range, 23-81 years). Of the 108 patients, 77% had FGFR2 gene fusions. All patients in the study were treated with infigratinib 125 mg orally for 21 days of each 28-day cycle, and treatment continued until unacceptable toxicity or disease progression. Patients were also administered prophylaxis with the oral phosphate binder sevelamer.

The coprimary end points explored in the study were objective response rate (ORR) by independent central review per RECIST v1.1 and duration of response (DOR). The study also investigated progression-free survival (PFS), disease control rate, overall survival, safety, pharmacokinetics as secondary end points. Three cohorts were included in the study, and results presented during ASCO GU focused on cohort 1 of patients with FGFR2 gene fusions or rearrangements who did not receive a prior FGFR inhibitor.


At a median follow-up of 10.6 months (range 1.1-55.9 months), treatment with infigratinib achieved an ORR of 23.1% (95% CI, 15.6%-32.2%) per blinded independent central review, which included a complete response in 1 patient and partial responses in 24 patients. In addition, 66 patients achieved stable disease on treatment with infigratinib while 11 patients had progressive disease. Response to treatment was unknown for 6 patients. The median DOR observed in the study was 5.0 months (range, 0.9-19.1 months). Javle et al noted that of the responders, 32.0% had a DOR of 6 months or longer. Infigratinib also achieved a median PFS of 7.3 months (95% CI, 5.6-7.6 months) and a median OS of 12.2 months (95% CI, 10.7-14.9)

A subgroup analysis compared the outcomes of infigratinib treatment in patients treated in the second-line setting versus the third-line or later settings. Among patients treated in the second-line setting, the ORR was 34% (95% CI, 21.2-48.8) compared with 13.8% (95% CI, 6.1-25.4) for those treated in lines 3 to 8. Among the 50 patients treated in the second-line setting, 17 patients achieved PRs, 27 had SD, 4 had, and 2 had unknown responses for a DCR of 88.0% (95% CI, 75.7%-95.5%). Of the 58 patients treated in later-line settings, there was a CR in 1 patient, PRs in 7 patients, and unknown response in 4 patients. The DCR in the group was 81.0% (95% CI, 68.6-90.1%).

In the overall study population, treatment-emergent adverse events were seen in >20% of patients. The most common any-grade TEAEs included hyperphosphatemia, stomatitis, fatigue, and alopecia. Management of on-target toxicities consisted of dose interruptions, dose reductions, supportive care, dietary modifications, and concomitant medications. Gastrointestinal toxicities were uncommon in the study.

Based on the phase 2 data, Javle et al consider infigratinib a new therapeutic option for patients with FGFR2-positive cholangiocarcinoma.

“This is an important milestone for patients diagnosed with FGFR2-fusion-driven cholangiocarcinoma who have recurred after first-line therapy and are in need of targeted options for further treatment,” said Susan Moran, MD, MSCE, chief medical officer for QED. “Based on the efficacy seen to date, our team believes infigratinib possesses promise for a range of FGFR-driven conditions, including other cancers. We will continue to evaluate its safety and efficacy in these areas of unmet need.”


1. BridgeBio Pharma’s affiliate QED Therapeutics and partner Helsinn Group announce FDA approval of TRUSELTIQ™ (infigratinib) for patients with cholangiocarcinoma. News release. BridgeBio Pharma. May 28, 2021. Accessed May 28, 2021. https://bit.ly/3bZn3ac 

2. Javle MM, Roychowdhury S, Kelley RK et al. Final results from a phase II study of infigratinib (BGJ398), an FGFR-selective tyrosine kinase inhibitor, in patients with previously treated advanced cholangiocarcinoma harboring an FGFR2 gene fusion or rearrangement. J Clin Oncol. 2021; 39 (suppl 3). doi: 10.1200/JCO.2021.39.3_suppl.265