Futibatinib Earns Breakthrough Therapy Designation for FGFR2+ Cholangiocarcinoma


Phase 2 trial data support the FDA breakthrough therapy designation for futibatinib in cholangiocarcinoma tumors positive for FGFR2 gene fusions and rearrangements.

Breakthrough therapy designation was granted to the agent futibatinib (TAS-120) by the FDA for the treatment of patients with previously treated locally advanced or metastatic cholangiocarcinoma harboring FGFR2 gene fusions and other rearrangements, announced the company responsible for developing the agent, Taiho Oncology, Inc.1

This decision was based on positive results of the phase 2 FOENIX-CCA2 trial (NCT02052778), which examined the agent in patients with advanced solid tumors with and without FGF/FGFR-related abnormalities. Groups 1 through 4 of 8 total groups receiving futibatinib therapy on the trial are specific to cholangiocarcinoma tumors. Results of the trial are scheduled for presentation at the upcoming American Association for Cancer Research (AACR) Annual Meeting 2021, taking place April 9-14, 2021.

“We are very pleased with the designation of futibatinib as a breakthrough therapy by the FDA,” Teruhiro Utsugi, PhD, senior managing director at Taiho, said in a press release. “We will continue to advance our research and development efforts to deliver futibatinib, discovered in our research center, as one of the agents which may benefit cholangiocarcinoma patients around the world waiting for new treatment options.”

Data from the FOENIX-CCA2 trial in patients with intrahepatic cholangicarcinoma harboring FGFR2 gene fusions and other rearrangements was presented at the American Society of Clinical Oncology 2020 Virtual Scientific Program.2 In 67 response-evaluable patients, 1 (1.5%) had a complete response (CR) and 24 (35.8%) had a partial response (PR), for an objective response rate (ORR) of 37.3% (95% CI, 25.8%-50.0%). The rate of stable disease (SD) was 44.8% and only 11 patients (16.4%) had progressive disease.

At a median follow-up of 11.4 months, the median progression-free survival (PFS) in all patients was 7.2 months (95% CI, 4.9-15.2). Rates at 3, 6, 9, and 12 months were 81.4% (95% CI, 69.6%-89.0%), 61.0% (95% CI, 47.5%-72.0%), 46.2% (95% CI, 32.5%-58.9%), and 39.4% (95% CI, 25.1%-53.4%), respectively.

The median time to response was 2.5 months (95% CI, 1.0-6.7) and the median response duration was 8.3 months (95% CI, 6.2-not reached). At the data cutoff, 25 patients (37%) remained on therapy, accounting for 1 patient with a CR, 14 reaching a PR, and 10 achieving SD.

Treatment-related adverse events (TRAEs) were noted in all patients, with serious treatment-related events occurring in 10.4%. Modification to the study drug due to TRAEs occurred in 65.7%, including drug interruptions (55.2%), dose reductions (50.7%), and drug discontinuation in 1 patient (1.5%) due to oral dysesthesia, pharyngeal inflammation, and stomatitis.

The investigators concluded that these data highlight the importance of molecular testing in this tumor type.

“We have come to learn over the past decade that intrahepatic cholangiocarcinoma is a molecularly heterogeneous tumor with nearly 50% of tumors harboring an actionable gene signature,” said Lipika Goyal, MD, of Massachusetts General Hospital, who presented the data at ASCO 2020. “Our patients can potentially benefit from personalized medicine approaches.”

Futibatinib is potent, selective, and irreversible small-molecule inhibitor of FGFR 1/2/3/4 that is administered by the oral route. The mechanism of action of futibatinib is its selective and irreversible linking to the ATP binding pocket of FGFR1-4, which results in inhibition of FGFR-mediated signal transduction pathways, reduced proliferation of tumor cells, and upregulated tumor cell death in tumors with these aberrations.


1. FDA Grants Breakthrough Therapy Designation for Taiho Oncology's Futibatinib for Treatment of Advanced Cholangiocarcinoma. News release. Tahio Oncology Inc. April 1, 2021. Accessed April 1, 2021. https://bit.ly/3fClcKT

2. 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

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