Futibatinib Demonstrates Promising Responses in FGFR2+ Intrahepatic Cholangiocarcinoma


In an interim analysis of a subset of patients with intrahepatic cholangiocarcinoma harboring FGFR2 fusions/rearrangements, futibatinib was shown to be efficacious and tolerable.

In an interim analysis of a subset of patients with intrahepatic cholangiocarcinoma (iCCA) harboring FGFR2 fusions/rearrangements, futibatinib (TAS-120) was shown to be efficacious and tolerable, according to a poster presentation at the European Society of Medical Oncology Virtual Congress 2020.

Investigators recorded an objective response rate (ORR) of 37.3% (95% CI, 25.8-50.0) in this analysis of 67 patients with at least 6 months of follow-up. One (1.5%) patient had complete response and 24 (35.8%) had partial response.1

Futibatinib is an oral, small molecule inhibitor of FGFR1-4. FGFR2 fusions occur in 10% to 20% of patients with iCCA. Patients with these alternations have a 5-year survival rate of 24%. There is no standard treatment for advanced disease after first-line chemotherapy.2

Responses were durable, lasting a median of 8.3 months, and 37% of patients remain on treatment. Investigators observed objective responses across patient subgroups, regardless of the number of prior treatment regimens and in patients with co-occurring genetic alterations in TP53, IDH1, and PI3K genes.

The disease control rate was 82.1% ­(95% CI, 70.8-90.4). Median time to response was 2.5 months (range, 1.4-2.7). The median duration of response (DOR) was 8.3 months (95% CI, 6.2 to not evaluable).

The median progression-free survival (PFS) was 7.2 months (95% CI, 4.0-15.2). At 6-months, PFS was 61% (95% CI, 47.5-72.0) and the overall survival (OS) was 86% (95% CI, 74.7-92.4).

FOENIX-CCA2 (NCT02052778) is an ongoing global, open-label phase 2 study of patients with unresectable locally advanced or metastatic iCCA harboring an FGFR2 fusion or rearrangement. A total of 103 patients were enrolled across 36 international sites from April 2018 to November 2019. Median follow-up in this planned analysis (database lock March 30, 2020) was 11.4 months. Investigators identified FGFR2 fusion in 55 patients (82%).

The primary endpoint was ORR assessed by independent central radiology review per RECIST v1.1, confirmed by a second tumor assessment 4 to 6 weeks after the initial response. Duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), and safety were secondary endpoints

Investigators noted the safety profile observed was consistent for this drug class. All patients experienced treatment-related adverse effects (TRAE) and 38 (57%) experienced a grade 3 TRAE.

Sseven (10%) patients reported serious TRAEs. Migraine (n = 2) was the only serious TRAE reported in more than 1 patient. Overall, 44 patients (66%) had a dosing modification because of a TRAE. There were 37 patients (55%) and 34 patients (51%) who required dosing interruption and dose reduction, respectively.

Eighteen (27%) patients experienced grade 3 or higher hyperphosphatemia. All cases resolved with medication and no patients discontinued treatment because of hyperphosphatemia.

Thirty-six patients (54%) discontinued because of clinical or radiological disease progression; no patients died while on treatment. Four patients discontinued treatment because AEs. One patient experienced stomatitis, oral dysesthesia, and pharyngeal inflammation attributed to treatment.

This trial also included a phase 1 dose-escalation study, which established 20 mg once daily futibatinib as the maximum tolerated dose.3 Antitumor activity of futibatinib was also demonstrated across patients with various advanced tumor types (including cholangiocarcinoma) with a range of FGFR alterations.

A phase 3 study, FOENIX-CCA3 (NCT04093362), of futibatinib versus gemcitabine–cisplatin in the first-line setting is underway.4 This is an open-label, multinational, parallel 2-arm, randomized study of patients with advanced, metastatic, or recurrent unresectable iCCA harboring FGFR2 gene rearrangements. The trial will enroll 216 patients. The primary endpoint is PFS, with secondary outcomes endpoints of ORR, DCR, and OS, as well as safety and tolerability.

Futibatinib is also being studied in a phase 2 trial (NCT04024436) in patients locally advanced/metastatic breast cancer harboring FGFR gene amplifications.5 This is an open-label, non-randomized that will recruit 168 patients and assess ORR, clinical benefit rate, and 6-month PFS.


  1. Bridgewater JA, Meric-Bernstam F, Hollebecque A, Valle JW, 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). Poster. European Society of Medical Oncology (EMSO) Virtual Congress 2020; September 17-21, 2020. Abstract #4493.
  2. Goyal L, Meric-Bernstam F, Hollebecque A, Valle JW, 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(15):108. doi: 0.1200/JCO.2020.38.15_suppl.108
  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. https://bit.ly/3kp1zoP
  5. A study of TAS-120 in patients with metastatic breast cancer. ClinicalTrials.gov. Updated March 5, 2020. https://bit.ly/2RDgiAd
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