Clinical trialPhase 2Bile duct and gallbladder cancer (biliary tract cancer)

Futibatinib for FGFR2-Rearranged Intrahepatic Cholangiocarcinoma

N Engl J Med · 2023103 patients

Goyal L, Meric-Bernstam F, Hollebecque A, et al. N Engl J Med. 2023. 388:228-239

Study type: Clinical trial
Study name: FOENIX-CCA2
Phase: Phase 2
Design: Multinational, open-label, single-group trial
Sample size: 103 patients
Source: N Engl J Med · 2023
Trial registration: NCT02052778

In plain words

People with bile duct cancer inside the liver with a change in the FGFR2 gene, whose disease had grown after earlier treatment, took futibatinib tablets every day. The tumour shrank in about 4 in 10 patients, and in most of them this lasted several months. The most common side effect was a rise in blood phosphate, and quality of life was maintained.

Key results

42%

Objective response

43 of 103; 95% CI 32–52

9.7 months

Median duration of response

9.0 months

Median progression-free survival

Median follow-up 17.1 months

21.7 months

Median overall survival

Dose and schedule cards

Futibatinib (FGFR2)

Previously treated, unresectable or metastatic intrahepatic cholangiocarcinoma with an FGFR2 fusion or rearrangement (FDA, accelerated approval)Cycle length: ContinuousOn the page “Bile duct and gallbladder cancer (biliary tract cancer)” · After progression on first line: chemotherapy and targeted therapy

Previously treated, unresectable or metastatic intrahepatic cholangiocarcinoma with an FGFR2 fusion or rearrangement (FDA, accelerated approval)

Drug	Dose	Route	Schedule
Futibatinib	20 mg once daily	Oral	Daily, continuously

Cycle length: Continuous
Duration: Until progression or unacceptable toxicity

Dose source: FDA label. Dose reductions: 16 mg, then 12 mg; intolerance of 12 mg → discontinue. Eye examination with OCT before starting, every 2 months for the first 6 months, then every 3 months, and urgently for visual symptoms; monitor phosphate. In FOENIX-CCA2, treatment-related grade 3 hyperphosphataemia occurred in 30%.

On the page “Bile duct and gallbladder cancer (biliary tract cancer)” · After progression on first line: chemotherapy and targeted therapy

Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.

Treatment arms and regimens

1Futibatinib

Oral futibatinib 20 mg once daily, continuously.

Source of the regimen details: Abstract of the paper (N Engl J Med 2023) and the FDA label for Lytgobi

Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.

Study population

Patients with unresectable or metastatic intrahepatic cholangiocarcinoma with an FGFR2 fusion or rearrangement whose disease had progressed after one or more previous lines of systemic therapy (excluding FGFR inhibitors).

Endpoints

Primary endpoint: objective response (partial or complete response) by independent central review. Secondary endpoints: duration of response, progression-free survival, overall survival, safety and patient-reported outcomes.

Safety and side effects

The most common treatment-related grade 3 adverse events were hyperphosphataemia (30%), increased aspartate aminotransferase (7%), stomatitis (6%) and fatigue (6%). Treatment-related adverse events led to permanent discontinuation of futibatinib in 2%, and there were no treatment-related deaths. Quality of life was maintained during treatment.

Clinical significance and place in guidelines

FOENIX-CCA2 was the basis of FDA accelerated approval of futibatinib, a covalent FGFR1–4 inhibitor, for previously treated intrahepatic cholangiocarcinoma with an FGFR2 fusion or rearrangement. ESMO 2025 recommends futibatinib (ESMO-MCBS v1.1 score 3) after one or more lines of therapy [III, A; ESCAT I-B].

Limitations

A single-group trial without a comparison group; only intrahepatic cholangiocarcinoma was included, and patients had not received an FGFR inhibitor before.

Original article (DOI)PubMed ClinicalTrials.gov

This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.