FDA Grants Breakthrough Therapy Designation for Cholangiocarcinoma Treatment Futibatinib

The FDA has granted Breakthrough Therapy Designation to futibatinib, a covalently binding FGFR inhibitor for the treatment of patients with previously treated locally advanced or metastatic cholangiocarcinoma harboring FGFR2 gene rearrangements including gene fusions.

The FDA has granted Breakthrough Therapy Designation to futibatinib (TAS-120), a covalently binding FGFR inhibitor for the treatment of patients with previously treated locally advanced or metastatic cholangiocarcinoma harboring FGFR2 gene rearrangements including gene fusions, according to a press release by Taiho Oncology, Inc.1

The designation is based on the results of the phase 2 FOENIX-CCA2 trial (NCT02052778), for which results will be presented at the upcoming American Association for Cancer Research (AACR) Annual Meeting 2021. Futibatinib works by selectively and irreversibly binding to the ATP binding pocket of FGFR-1, which inhibits FGFR-mediated single transudation pathways. This reduces tumor cell proliferation and increases tumor cell death.1

FOENIX-CCA2 has an actual enrollment of 386 patients and was made up of 1 arm. In the single arm, patients received futibatinib orally over a 21-day cycle. The primary outcome of the phase 2 study was overall response rate (ORR). Secondary outcomes included duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), patient-reported outcomes (PROs), and overall survival (OS).

In order to participate, patients were required to be 18 years old or older and must have been treated with and failed at least 1 prior systemic gemcitabine and platinum-based chemotherapy for the advanced disease. Additionally, patients must have adequate organ function. Patients with evidence of non-tumor related alteration of calcium-phosphorus homeostasis or significant ectopic mineralization/calcification are not eligible to participate.

Of the 103 patients enrolled in phase 2, 67 patients were included in the interim analysis of the FOENIX-CCA2 study. Of these patients, 82.1% had a tumor harboring an FGFR2 mutation. Of the patients evaluated, 44% had 1 prior line of treatment, 28.4% had 2 prior lines, and 26.9% had 3 prior lines. The ORR was 34.3% and the DCR was 76.1%. The median time to response was 1.6 months with a median DOR of 6.2 months.

Overall, safety was consistent with the class of drug. All patients experienced treatment-related adverse effects (TRAE) and TRAEs were grade 3 in 57% of patients. Serious TRAEs occurred in 10% of patients, but all but 1 events only occurred once. Hyperphosphatemia was the most common grade 3 or less adverse event (AE), bu all cases were resolved with medication and no patients discontinued treatment due to the occurrence of hyperphosphatemia.The rate of any-cause grade 3 or greater AE was 73.1%. Dose delay was required in 65% of patients and dose reduction was required in 53.7% of patients. A total of 6% of patients had to discontinue treatment due to AEs.2

"Patients living with locally advanced and metastatic cholangiocarcinoma, or bile duct cancer, currently have a poor prognosis,1,2 particularly since there is no standard treatment after the failure of first-line chemotherapy3," said Martin J. Birkhofer, MD, senior vice president and chief medical officer, Taiho Oncology, Inc in a press release. "We are pleased that the FDA has recognized the potential benefit of futibatinib in previously treated CCA patients. We look forward to continued dialogue with FDA and other Health Authorities as we work toward global availability of futibatinib for cholangiocarcinoma patients."

Futibatinib was initially granted by Orphan Drug Status by the FDA in May of 2018. It has not been approved by any authority for the treatment of patients outside of investigational purposes.

1. FDA grants breakthrough therapy designation for Taiho Oncology’s futibatinib for treatment of advanced cholangiocarcinoma. News release. Taiho Oncology, Inc. April 1, 2021. Accessed April 1, 2021. https://bit.ly/31ArpyM
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 (suppl15):108-108. doi: 10.1200/JCO.2020.38.15_suppl.108