FDA Withdraws Infigratinib Approval Status in FGFR2+ Cholangiocarcinoma

Infigratinib originally earned accelerated approval from the FDA as a treatment for this patient population in May 2021.

The FDA has withdrawn accelerated approval status for infigratinib (Truseltiq) as a therapy for patients with previously treated, locally advanced or metastatic, unresectable cholangiocarcinoma harboring FGFR2 fusions or rearrangements, according to a news release from the agency.¹

As part of accelerated approval status requirements, developers needed to verify the agent’s clinical benefit via confirmatory postmarketing trials. Developers voluntarily requested the therapy’s withdrawal from the market due to issues associated with enrolling patients in a confirmatory clinical trial intended to evaluate infigratinib as a treatment for first-line cholangiocarcinoma. Based on the difficulties pertaining to patient recruitment, developers determined that it would no longer be commercially reasonable to distribute infigratinib as a therapy for second-line disease.

Infigratinib originally earned accelerated approval from the FDA as a treatment for this patient population in May 2021.² The regulatory agency based its accelerated approval of the agent on findings from a phase 2 clinical trial (NCT02150967).

According to findings published in The Lancet Gastroenterology & Hepatology, treatment with infigratinib elicited an objective response rate (ORR) of 23.1% (95% CI, 15.6%-32.2%) per blinded independent central review (BICR) among 108 evaluable patients.³ Partial responses (PRs) were reported in 22%, and 1% of patients had a complete response (CR). Additionally, the median duration of response (DOR) was 5.0 months (IQR, 3.7-9.3).

Infigratinib yielded a median progression-free survival (PFS) of 7.3 months (95% CI, 5.6-7.6). Additionally, the median overall survival (OS) was 12.2 months (95% CI, 10.7-14.9).

Any-grade treatment-emergent adverse effects (TEAEs) and treatment-related AEs (TRAEs), respectively, occurred in 99% and 96% of patients. The most common types of TEAEs and TRAEs of any grade included hyperphosphatemia (77% vs , 74%), stomatitis (55% vs , 51%), fatigue (40% vs %, 29%), and alopecia (38% vs , 32%). Investigators reported that 5 patients had died due to cholangiocarcinoma. One patient with grade 4 sepsis not associated with study treatment died 36 days following their last dose.

“These mature results from our study show that infigratinib had meaningful clinical activity in patients with previously treated cholangiocarcinoma harboring FGFR2 fusions or rearrangements, half of whom were being treated in the third or later line,” the study authors wrote.³ “Infigratinib was one of the first FGFR inhibitors to enter early-phase clinical trials and this investigation was done at a time when very few patients with gastrointestinal cancer underwent routine next-generation sequencing.”

In this open-label, single-arm phase 2 study, 108 patients with FGFR2 fusions or rearrangements were assigned to receive infigratinib orally once daily at 125 mg for 21 days of a 28-day cycle. Study treatment continued until progressive disease, intolerance, withdrawal of consent, or death.

The trial’s primary end point was ORR per BICR based on RECIST v1.1 criteria. Secondary end points included the disease control rate, time to response, PFS, OS, safety, and tolerability.

Patients 18 years and older with histologically or cytologically confirmed cholangiocarcinoma and FGFR2 fusions or rearrangements as confirmed via local or central laboratory assessment were eligible for enrollment on the trial. Additional eligibility criteria included having prior treatment with gemcitabine for metastatic or advanced disease, progression following the most recent prior line of therapy, an ECOG performance status of 0 or 1, and evidence of measurable disease per RECIST v1.1 guidelines.

Those who had prior treatment with mitogen-activated protein kinase inhibitors, infigratinib, or another selective FGFR inhibitor were ineligible for enrollment. Patients were also unsuitable for study entry if they had neurological symptoms requiring management with corticosteroids or evidence of extensive tissue calcification.

References

1. WITHDRAWN: FDA grants accelerated approval to infigratinib for metastatic cholangiocarcinoma. News release. FDA. May 17, 2024. Accessed May 20, 2024. https://tinyurl.com/2vknm675
2. BridgeBio Pharma’s affiliate QED Therapeutics and partner Helsinn Group announce FDA approval of Truseltiq (infigratinib) for patients with cholangiocarcinoma. News release. BridgeBio Pharma, Inc. May 28, 2021. Accessed May 20, 2024. https://bit.ly/3uy5LHB
3. 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. doi:10.1016/S2468-1253(21)00196-5