FDA Approves Futibatinib for FGFR2+ Advanced Cholangiocarcinoma

Findings from the TAS-120-101 study have led the FDA to approve futibatinib for the treatment of patients with FGFR2-positive advanced cholangiocarcinoma.

The FDA has granted an accelerated approval to futibatinib (Lytgobi) for the treatment of patients with previously treated locally advanced or metastatic cholangiocarcinoma who harbor FGFR2 gene rearrangement, including gene fusions.1,2

"Lytogobi is an effective, well-tolerated therapy for patients with intrahepatic CCA that can be taken orally," said Tim Whitten, president and chief executive officer of Taiho Oncology, Inc, in a press release. "This approval is an important milestone for patients and may provide hope for improved outcomes. As someone whose family has been impacted by cholangiocarcinoma, I'm acutely aware of the impact this disease can have on the patient and their loved ones."

Approval for futibatinib is supported by findings from the TAS-120-101 (NCT02052778), which include 132 patients with previously treated, unresectable, locally advanced, or metastatic intrahepatic cholangiocarcinoma harboring a FGFR2 gene fusion or other rearrangement. The study showed that futibatinib acheived an objective response rate (ORR) of 42% (95% CI, 32-52), with a 9.7-month (95% CI: 7.6, 17.1) median duration of response (DOR).

In the study, futibatinib lead to adverse events (AEs) with the most common being nail toxicity, musculoskeletal pain, constipation, diarrhea, fatigue, dry mouth, alopecia, stomatitis, abdominal pain, dry skin, arthralgia, dysgeusia, dry eye, nausea, decreased appetite, urinary tract infection, palmar-plantar erythrodysesthesia syndrome, and vomiting.

The agent was also studied in the phase 2b FOENIX-CCA2 study (NCT02052778), which evaluated the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and anti-tumor activity of the fibroblast growth factor receptor (FGFR) inhibitor in patients with locally advanced or metastatic unresectable intrahepatic cholangiocarcinoma with FGFR gene rearrangements.3

Futibatinib was previously granted breakthrough therapy designation by the FDA in 2021 and was accepted for priority review by the FDA in March 2022 for the treatment of patients with previously treated locally advanced metastatic cholangiocarcinoma based on the results which were presented at the 2021 American Association for Cancer Research Meeting

The open-label, non-randomized, pivotal phase 2b FOENIX-CCA2 study assessed the treatment in 103 patients who received futibatinib at 20 mg orally once daily over a 21-day cycle until disease progression or unacceptable toxicity. There were a maximum of 2 dose reductions, dropping to 16 mg and then to 12 mg, allowed in order for participants to manage any treatment-emergent adverse effects (AEs).

Eligibility for enrollment was open to patients with an ECOG performance status of 0 or 1, measurable disease per RECIST v1.1 criteria, those who have previously received gemcitabine and platinum-based chemotherapy, and those who have experienced disease progression after at least 1 systemic treatment.

The primary outcome of the trial was ORR with secondary outcomes consisting of DOR, disease control rate (DCR), progression-free survival (PFS), patient-reported outcomes (PROs), and overall survival (OS).

Findings of the trial reveal the agent to demonstrate frequent and durable objective responses in the patient population. These results were observed irrespective of patients’ baseline characteristics, molecular alteration, or co-mutation. Further, AEs reported with the agent appeared manageable.

Futibatinib achieved an ORR of 41.7% per independent central review with a 9.7-month median DOR. Notably, 72% of patients who responded to treatment continued for 6 months or more.

At the time of the data cutoff, October 1, 2020, a total of 70% of patients had discontinued treatment. Futibatinib resulted in a DCR of 82.5%, and a median PFS of 9.0 months. Further, the median OS shown with the agent was 21.7 months, and the 12-month OS rate was 72%.

The ORR benefit with futibatinib was shown to be consistent across all patient subsets analyzed, including patients who were 65 years of age and older (65.2%) and those who previously received 2 or more treatments (38.7%).

Data from exploratory biomarker analyses also showed the ORR achieved with futibatinib to be consistent in those whose tumors harbored FGFR2 fusions (43.8%), those with other FGFR2 rearrangements (34.8%), those with BICC1 (41.7%), and those with non-BICC1(44.6%) fusion partners. There were no notable differences in ORR observed in those with co-occurring genetic alterations, including TP53 comutations (38.5%).

The most common treatment-related AEs (TRAEs) found in patients included hyperphosphatemia (85%), alopecia (33%), and dry mouth (30%). The most frequent grade TRAE was hyperphosphatemia (30%). Additionally, a total of 8% of patients noted grade 1/2 retinal disorders had occurred.

Overall, the TRAEs seen in patients were tolerable. However, dose interruptions occurred in 50% of patients, dose reductions were required for 54%, and 2 patients discontinued treatment as a result of TRAEs.


1. FDA grants accelerated approval to futibatinib for cholangiocarcinoma. FDA.gov. September 30, 2022. Accessed September 30, 2022. https://bit.ly/3LXIKIn

2. FDA approves Taiho's Lytgobi® (futibatinib) tablets for previously treated, unresectable, locally advanced or metastatic intrahepatic cholangiocarcinoma. Taiho Oncology. New release September 30, 2022. Accessed September 30, 2022.

2. Goyal L, Meric-Bernstam F, Hollebecque A, et al. Abstract CT010: Primary results of phase 2 FOENIX-CCA2: The irreversible FGFR1-4 inhibitor futibatinib in intrahepatic cholangiocarcinoma (iCCA) with FGFR2 fusions/rearrangements. CancerRes. 2021;81 (suppl 13): CT010. doi: 10.1158/1538-7445.AM2021-CT010