FDA Grants Priority Review to Futibatinib for FGFR2+ Advanced Cholangiocarcinoma

The FDA has granted priority review to a new drug application seeking the approval of futibatinib in the treatment of patients with previously treated locally advanced or metastatic cholangiocarcinoma harboring FGFR2 gene rearrangements, including gene fusions.

The FDA has granted priority review to a new drug application (NDA) seeking the approval of futibatinib (TAS-120) in the treatment of patients with previously treated locally advanced or metastatic cholangiocarcinoma harboring FGFR2 gene rearrangements, including gene fusions.1

The application is based on findings from the phase 2b FOENIX-CCA2 trial (NCT02052778), in which the agent was found to elicit an objective response rate (ORR) of 41.7% per independent central review (ICR) with a median duration of response (DOR) of 9.7 months.2 Notably, 72% of those who responded to treatment continued to respond for 6 months or longer.

Under the Prescription Drug User Fee Act, the regulatory agency will decide on the NDA by September 30, 2022.

“Given the lack of an accepted standard chemotherapy following the failure of first-line treatment, futibatinib could represent a significant opportunity for a targeted therapy in this subset of patients with cholangiocarcinoma, which has driven our pursuit with this investigational compound,” Volker Wacheck, vice president of Clinical Development at Taiho Oncology, Inc., stated in a press release. “We look forward to working with the FDA as they consider the application for futibatinib under priority review.”

A highly selective irreversible FGFR1-4 inhibitor, futibatinib forms a covalent adduct with a cysteine residue in the P-loop of the FGFR, and a potential benefit with these kinds of inhibitors is that they can result in better potency and selectivity.3

The open-label, multicenter, phase 2b trial enrolled patients with unresectable or metastatic intrahepatic cholangiocarcinoma harboring FGFR2 fusions or other rearrangements. Patients needed to have an ECOG performance status of 0 or 1, measurable disease per RECIST v1.1 criteria, have previously received gemcitabine and platinum-based chemotherapy, and experienced disease progression after at least 1 systemic treatment. Patients could not have previously received a FGFR inhibitor.

Study participants received oral futibatinib at a once-daily dose of 20 mg, given continuously as a part of 21-day treatment cycles. Treatment was administered until progressive disease, drug intolerance, withdrawn consent, or death. A maximum of 2 dose reductions, dropping to 16 mg and then to 12 mg, were allowed to manage any treatment-emergent adverse effects (AEs).

The primary end point of the trial was ORR per ICR, and a key secondary end point was DOR. Other secondary end points comprised disease control rate (DCR), progression-free survival (PFS), and safety.

A total of 103 patients were enrolled to the trial. Fifty-six percent of participants were female and 53% had previously received 2 or more lines of treatment. Moreover, 78% had tumors that harbored FGFR2 fusions, and 22% had FGFR2 rearrangements.

At a data cutoff date of October 1, 2020, 70% of patients had discontinued treatment. Data presented during the 2021 AACR Annual Meeting showed that futibatinib resulted in a DCR of 82.5%, and a median PFS of 9.0 months. Moreover, the median overall survival (OS) with the agent was noted to be 21.7 months, and the 12-month OS rate was 72%.

Additionally, the ORR benefit provided with futibatinib proved to be consistent across all patient subsets analyzed, including those who were aged 65 years and older (65.2%) and those who previously received 2 or more treatments (38.7%).

Moreover, data from exploratory biomarker analyses indicated that the ORR achieved with futibatinib was consistent in those whose tumors harbored FGFR2 fusions (43.8%) and those with other FGFR2 rearrangements (34.8%), as well as in those with BICC1 (41.7%) and non-BICC1 (44.6%) fusion partners. No notable differences in ORR were observed in those with co-occurring genetic alterations, including TP53 comutations (38.5%).

Regarding safety, common treatment-related AEs (TRAEs) with the agent included hyperphosphatemia (85%), alopecia (33%), and dry mouth (30%). The most common TRAE that were grade 3 or higher in severity was hyperphosphatemia (30%), and this was resolved with appropriate management. Eight percent of patients experienced retinal disorders with futibatinib, although these effects were grade 1 or 2. The only serious adverse reaction reported in more than 1 patient enrolled to the trial was migraine (1.9%).

Investigators managed TRAEs with dosing interruptions in 50% of patients, and dosing reductions in 54% of patients. Two total patients discontinued treatment with the agent due to toxicities. Notable, no treatment-related deaths were reported.

Quality-of-life data presented during the 2021 ASCO Annual Meeting showed that physical, cognitive, and emotional functioning, as well as overall health status were maintained among those with advanced disease who received futibatinib.4

Specifically, the mean EORTC QLQ-C30 scores on global health status and functional scales were maintained from baseline to cycle 13, and no clinically meaningful changes were reported. Mean EQ VAS scores were sustained from baseline to cycle 13, and values were maintained within the population norm range across 20 countries. Moreover, changes from baseline in individual EQ-5D-3L dimensions indicated that 72% to 94% of patients’ status either remained the same or improved over time.

“This is an important step toward our goal to deliver futibatinib to patients awaiting potential new treatment options,” Teruhiro Utsugi, senior managing director at Taiho Pharmaceutical, added in the press release. “The Taiho group, working as one, will continue to do its utmost to deliver this agent to those in need.”

In April 2021, the FDA granted a breakthrough therapy designation to futibatinib for the treatment of patients with previously treated, locally advanced or metastatic cholangiocarcinoma that harbors FGFR2 gene rearrangements, including fusions.5


  1. US Food and Drug Administration (FDA) accepts for priority review Taiho Oncology’s new drug application for futibatinib for cholangiocarcinoma. News release. Taiho Oncology, Inc.; March 30, 2022. Accessed March 30, 2022. https://prn.to/3uEZKee
  2. Goyal Lipika, 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. Cancer Res. 2021;81(suppl 13):CT010. doi:10.1158/1538-7445.AM2021-CT010
  3. Goyal L, Meric-Bernstam F, Hollebecque A, et al. FOENIX-CCA2: a phase II, open-label, multicenter study of futibatinib in patients (pts) with intrahepatic cholangiocarcinoma (iCCA) harboring FGFR2 gene fusions or other rearrangements. J Clin Oncol. 2020;38(suppl 15):108. doi:10.1200/JCO.2020.38.15_suppl.108
  4. Valle JW, Hollebecque A, Furuse J, et al. FOENIX-CCA2 quality of life data for futibatinib-treated intrahepatic cholangiocarcinoma (iCCA) patients with FGFR2 fusions/rearrangements. J Clin Oncol. 2021;39(suppl 15):4097. doi:10.1200/JCO.2021.39.15_suppl.4097
  5. FDA grants breakthrough therapy designation for Taiho Oncology’s futibatinib for treatment of advanced cholangiocarcinoma. News release. Taiho Oncology, Inc.; April 1, 2021. Accessed March 30, 2022. https://prn.to/3udl7RV
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