FOENIX-CCA2: Phase 2 Open-Label Study of Futibatinib in Patients with Intrahepatic Cholangiocarcinoma Harboring FGFR2 Gene Fusions

Futibatinib is a highly selective irreversible fibroblast growth factor receptor (FGFR)1-4 inhibitor, administered as a continuous once-daily oral regimen. The FOENIX-CCA2 phase 2 clinical trial was initiated after the results from a phase 1 dose-escalation/expansion study showed the tolerability and preliminary efficacy of futibatinib in patients with intrahepatic cholangiocarcinoma (CCA) and FGFR2 fusions.¹

Lipika Goyal, MD, MPhil, Medical Oncologist, Tucker Gosnell Center for Gastrointestinal Cancers, Massachusetts General Hospital, Boston, presented the phase 2 study results at the 2020 ASCO annual meeting.

“The interim analysis demonstrated that treatment with the covalently binding FGFR inhibitor futibatinib may lead to meaningful clinical benefit in patients with refractory [intrahepatic] CCA with FGFR2 gene fusions or other rearrangements,” said Dr Goyal. “In a disease with limited treatments, this drug could be an effective and well-tolerated option for patients and the oncologists that care for them.”

This single-arm, multicenter phase 2 clinical trial enrolled patients with locally advanced or metastatic unresectable intrahepatic CCA that harbors FGFR2 gene fusions or other rearrangements, disease progression after ≥1 lines of systemic therapy (including gemcitabine plus platinum-based chemotherapy), no previous FGFR inhibitor treatment, and an Eastern Cooperative Oncology Group performance status of 0 or 1.²

Patients received futibatinib 20 mg once daily until disease progression or unacceptable toxicity. The study’s primary end point was objective response rate (ORR) based on independent central radiology review. The secondary end points included disease control rate, duration of response, and safety.

A total of 103 patients were enrolled in the study. For this interim analysis, data were reported for the 67 (65%) patients with ≥6 months of follow-up. Of these 67 patients, 82.1% had tumors harboring an FGFR2 fusion. A total of 1, 2, or ≥3 previous therapy regimens were received by 44.8%, 28.4%, and 26.9% of patients, respectively.

The ORR was 34.3% (N = 23), all partial responses, and the disease control rate was 76.1%; assessment was pending for 8 patients. The median time to response to therapy was 1.6 months (range, 1.0-4.9 months), and the median duration of response was 6.2 months (range, 2.1-14.2 months).

The most common all-grade and grade ≥3 treatment-related adverse events were hyperphosphatemia (79.1%, 25.4%, respectively), diarrhea (37.3%, 0%), and dry mouth (32.8%, 0%).

All-cause grade ≥3 adverse events were reported in 73.1% of patients. A dosing delay was required in 65.7% of patients and 53.7% of patients required dose reduction; 6% of the patients discontinued treatment because of adverse events.

The investigators concluded that the preliminary data from this study demonstrate that futibatinib may be efficacious in patients with locally advanced or metastatic unresectable intrahepatic CCA harboring FGFR2 gene fusions that progress after ≥1 lines of chemotherapy.

References

1. Meric-Bernstam F, Arkenau H, Tran B, et al. Efficacy of TAS-120, an irreversible fibroblast growth factor receptor (FGFR) inhibitor, in cholangiocarcinoma patients with FGFR pathway alterations who were previously treated with chemotherapy and other FGFR inhibitors. Ann Oncol. 2018;29(suppl 5):Abstract O-001.
2. 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(15_suppl):Abstract 108.