FDA Grants Priority Review to Futibatinib for FGFR2+ Locally Advanced/Metastatic Cholangiocarcinoma

The FDA has accepted the new drug application (NDA) for futibatinib, seeking approval for the treatment of patients with previously treated locally advanced or metastatic cholangiocarcinoma who harbor FGFR2 gene rearrangement, including gene fusions.¹

According to an announcement by the drug developer Taiho Oncology, Inc. The application has been granted priority review by the FDA with a Prescription Drug User Fee Act target action date of September 30, 2022.

"Given the lack of an accepted standard chemotherapy following the failure of first-line treatment, futibatinib could represent a significant opportunity for a targeted therapy in this subset of patients with [cholangiocarcinoma], which has driven our pursuit with this investigational compound," said Volker Wacheck, vice president, clinical development, Taiho Oncology, Inc, in a press release. "We look forward to working with the FDA as they consider the application for futibatinib under priority review."

The NDA for futibatinib is supported by findings from the phase 2b FOENIX-CCA2 study (NCT02052778), which assessed the treatment in 103 patients with locally advanced or metastatic unresectable intrahepatic cholangiocarcinoma with GFR gene rearrangements. In the study 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).^1,2

Results reported in 2021 showed that the agent demonstrated frequent and durable objective responses in the patient population. These results were observed irrespective of patients’ baseline characteristics, molecular alteration, or co-mutation. Further, adverse events (AEs) reported with the agent appeared manageable.

Futibatinib achieved an ORR of 41.7% per independent central review with a 9.7-month median DOR. Moreover, 72% of responses lasted for more than 6 months.

In terms of safety, the most common treatment-related AEs (TRAEs) were hyperphosphatemia (85%), alopecia (33%), and dry mouth (30%). The most frequent grade TRAE was hyperphosphatemia (30%). Grade 1/2 retinal disorders were also noted also having occurred in 8% of patients. Overall, the TRAEs were tolerable, but dose interruptions occurred in 50% of patients and dose reductions were required for 54%. Two patients discontinued treatment as a result of TRAEs.

Based on these data, futibatinib was granted breakthrough therapy designation by the FDA in 2021 for the treatment of patients with previously treated locally advanced metastatic cholangiocarcinoma.

"This is a very important step towards our goal to deliver futibatinib to patients awaiting potential new treatment options," said Teruhiro Utsugi, senior manager, Taiho Pharmaceutical, in a statement. "The Taiho group, working as one, will continue to do its utmost to deliver this agent to those in need."

_REFERENCES:

_{1. U.S. Food and Drug Administration (FDA) accepts for priority review Taiho Oncology's new drug application for futibatinib for cholangiocarcinoma. News release. Taiho Oncology. March 30, 2022. Accessed March 30, 2022. https://bit.ly/3JWJfQY}

_{2. Goyal L, Meric-Bernstam F, Hollebecque A, et al. Abstract CT010: Primary results of phase 2 FOENIX-CCA2: The irreversible FGFR1-4 inhibitor futibatinib in intrahepatic cholangiocarcinoma (iCCA) with FGFR2 fusions/rearrangements. Cancer Res. 2021;81 (suppl 13): CT010. doi: 10.1158/1538-7445.AM2021-CT010}