Futibatinib Granted Breakthrough Therapy Designation for FGFR2+ Advanced Cholangiocarcinoma


The FDA has granted a breakthrough therapy designation to the FGFR inhibitor futibatinib for the treatment of patients with previously treated, locally advanced or metastatic cholangiocarcinoma that harbors FGFR2 gene rearrangements, including fusions.

The FDA has granted a breakthrough therapy designation to the FGFR inhibitor futibatinib (TAS-120) for the treatment of patients with previously treated, locally advanced or metastatic cholangiocarcinoma that harbors FGFR2 gene rearrangements, including fusions.1

The designation is based on safety and efficacy findings from the phase 2 FOENIX-CCA2 trial (NCT04093362), which will be revealed at the upcoming 2021 AACR Annual Meeting.

“Patients living with locally advanced and metastatic cholangiocarcinoma, or bile duct cancer, currently have a poor prognosis, particularly since there is no standard treatment after the failure of first-line chemotherapy,” Martin J. Birkhofer, MD, senior vice president and chief medical officer at Taiho Oncology, Inc., stated in a press release. “We are pleased that the FDA has recognized the potential benefit of futibatinib in previously treated [patients with] cholangiocarcinoma. We look forward to continued dialogue with FDA and other health authorities as we work toward global availability of futibatinib for [these] patients.”

Earlier data from an interim analysis of a subset of patients with FGFR2-positive intrahepatic cholangiocarcinoma from the trial showed that futibatinib was both efficacious and tolerable.2 The agent elicited an objective response rate (ORR) of 37.3% (95% CI, 25.8%-50.0%) in 67 patients with at least 6 months of follow-up; of those who responded to treatment, 1 achieved a complete response (1.5%) and 24 had a partial response (35.8%).

Moreover, responses proved to be durable, persisting for a median of 8.3 months; 37% remained on treatment at the time of data presentation. The median time to response was 2.5 months (range, 1.4-2.7) and the median duration of response (DOR) was 8.3 months (95% CI, 6.2–not evaluable). Futibatinib resulted in a disease control rate (DCR) of 82.1% (95% CI, 70.8%-90.4%) in this population.

Investigators also reported that objective responses were experienced across subgroups, irrespective of the number of previous regimens received and whether patients had co-occurring genetic alterations in TP53, IDH1, and PI3K genes.

The ongoing, global, open-label phase 2 trial enrolled patients with unresectable locally advanced or metastatic intrahepatic cholangiocarcinoma harboring a FGFR2 fusion or rearrangement. A total of 103 patients were enrolled to the trial between April 2018 and November 2019. The median follow-up for the planned analysis was 11.4 months. Eighty-two percent of patients were identified to have FGFR2 fusions.

The primary end point of the trial was ORR per independent central radiology review assessment and RECIST v1.1 criteria, confirmed by second tumor assessment 4 to 6 weeks following initial response to treatment. Secondary end points included DOR, DCR, progression-free survival (PFS), and safety.

Regarding safety, 57% of patients experienced a grade 3 treatment-related adverse effect (TRAE), while 10% experienced a serious TRAE. Migraine was the only serious TRAE that was reported in more than 1 patient (n = 2). Sixty-six percent of patients required a dosing modification due to a TRAE, 55% experienced a dose interruption, and 51% required dose reduction.

Twenty-seven percent of patients were observed to have hyperphosphatemia that was grade 3 or higher in severity; however, all cases resolved with medication and no patients needed to discontinue treatment because of the toxicity.

Moreover, 54% of patients discontinued treatment because of radiologic disease progression. Notably, no patients died while on treatment. Four patients discontinued treatment because of toxicities. One patient had stomatitis, oral dysesthesia, and pharyngeal inflammation that was determined to be linked with treatment.

The agent is also under examination in the phase 3 FOENIX-CCA trial (NCT04093362), where it is being compared with gemcitabine/cisplatin as a first-line treatment in patients with cholangiocarcinoma.3

The open-label, multinational, parallel, 2-arm trial will enroll patients with advanced, metastatic, or recurrent unresectable intrahepatic cholangiocarcinoma harboring FGFR2 rearrangements. A total of 216 patients are estimated to enroll. The primary end point of the research is PFS, while secondary end points included ORR, DCR, and overall survival, as well as safety and tolerability.

The agent is also under examination in an open-label, non-randomized phase 2 trial (NCT04024436) that is being done in patients with locally advanced/metastatic breast cancer harboring FGFR2 amplifications.4 The trial is expected to enroll 168 patients, and it will examine ORR, clinical benefit rate, and 6-month PFS.


  1. FDA grants breakthrough therapy designation for Taiho Oncology’s futibatinib for treatment of advanced cholangiocarcinoma. News release. Taiho Oncology, Inc. April 1, 2021. Accessed April 1, 2021. https://prn.to/3udl7RV
  2. Bridgewater J, Meric-Bernstam F, Hollebecque A, et al. Efficacy and safety of futibatinib in intrahepatic cholangiocarcinoma (iCCA) harboring FGFR2 fusions/other rearrangements: subgroup analyses of a phase II study (FOENIX-CCA2). Ann Oncol. 2020;31(4):S261-S262. doi:10.1016/j.annonc.2020.08.032
  3. Bahleda R, Meric-Bernstam F, Goyal L, Tran B, et al. Phase I, first-in-human study of futibatinib, a highly selective, irreversible FGFR1-4 inhibitor in patients with advanced solid tumors. Ann Oncol. 2020;S0923-7534(20)39928-2. doi:10.1016/j.annonc.2020.06.018.
  4. Futibatinib vs. gemcitabine-cisplatin chemotherapy as 1st-line treatment of patients with advanced cholangiocarcinoma (CCA) harboring FGFR2 gene rearrangements (FOENIX-CCA3). ClinicalTrials.gov. Updated February 7, 2020. Accessed April 1, 2021. https://clinicaltrials.gov/ct2/show/NCT04093362
  5. A study of TAS-120 in patients with metastatic breast cancer. ClinicalTrials.gov. Updated March 5, 2020. Accessed April 1, 2021. https://clinicaltrials.gov/ct2/show/NCT04024436

This article was originally published on OncLive as, "FDA Grants Breakthrough Therapy Designation to Futibatinib for FGFR2+ Advanced Cholangiocarcinoma."

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