Futibatinib Sustains Benefit in Advanced/Metastatic FGFR2+ iCCA

Phase 2 FOENIX-CCA2 study results further confirm the safety and efficacy of futibatinib for the treatment of previously treated patients with advanced/metastatic intrahepatic cholangiocarcinoma with FGFR2 fusions or rearrangements.

The durable efficacy and tolerability of futibatinib for the treatment of previously treated patients with advanced/metastatic intrahepatic cholangiocarcinoma (iCCA) who harbor FGFR2 fusions/rearrangements has been confirmed in the phase 2 FOENIX-CCA2 study (NCT02052778).1,2

Futibatinib achieved an objective response rate (ORR) of 42% (95% CI, 32%-52%), as assessed by independent review, and a median duration of response (DOR) of 9.7 months (95% CI, 7.6-17.0 months), supporting the continued FDA approval of futibatinib for the treatment of this patient population. The disease control rate (DCR) observed was 83% (95% CI, 74%-89%).

“Futibatinib is the first covalently binding selective FGFR inhibitor to gain FDA approval in oncology, and it stands as an effective treatment for patients with FGFR2 fusion or rearrangement positive cholangiocarcinoma. Molecular profiling is key for patients with cholangiocarcinoma as it can open therapeutic avenues,” Lipika Goyal, MD, MPhil, the lead investigator for FOENIX-CCA2 and previously a medical oncologist at Mass General Cancer Center and associate professor and director of Gastrointestinal Cancer at the Stanford School of Medicine, told Targeted Oncology™.

In phase 2 of the global, open-label FOENIX-CCA2 study, 103 patients with advanced/metastatic iCCA harboring FGFR2 fusions/rearrangements were enrolled and assessed for the primary end point of ORR per RECIST v1.1 by independent central review. The secondary end points were DOR, DCR, progression-free survival (PFS), overall survival (OS), safety, and patient-reported outcomes.

Notably, objective responses with futibatinib were observed across all protocol-specified subgroups, including in patients who were at least 65 years of age and those who received up to 3 prior lines of therapy.

At a median follow-up of 17.1 months (range, 10.1-29.6 months), futibatinib showed a median PFS of 9.0 months (95% CI, 6.9-13.1) as well as a median OS of 21.7 months (95% CI, 14.5-not reached). These survival results were similar to those observed in the primary analysis, which had an extended follow-up of 8.0 months.

Patient reported outcomes (PROs) to assess quality-of-life (QoL) showed that QoL was stable over a 9-month period. Moreover, investigators saw no meaningful differences in QoL from baseline, including in the physical, role, cognitive, emotional, or social domains. Also, there were no significant changes in health status across during the period patients were treated, according to the PROs analysis.

In terms of safety, at least 1 adverse event (AE) occurred in every patient in the study. The most common treatment-related AEs were hyperphosphatemia (85%), alopecia (33%), dry mouth (30%), diarrhea (28%), dry skin (27%) and fatigue (25%), which occurred in ≥ 25% of patients. Two percent of patients discontinued treatment because of treatment-related AEs. There were no new safety concerns in the study.

"The FOENIX-CCA2 trial results demonstrate that futibatinib is an effective treatment for FGFR2 fusion/rearrangement positive cholangiocarcinoma. Its activity and safety profile offer a new treatment in this setting. These data reinforce the importance of molecular profiling in cholangiocarcinoma and represent a step forward for patients facing a difficult disease," said Goyal, MD, in a press release.1


1. Taiho Oncology announces publication in The New England Journal of Medicine of pivotal data for futibatinib in previously treated patients with metastatic intrahepatic cholangiocarcinoma. News release. Taiho Oncology. January 18, 2023. Accessed January 25, 2023. https://prn.to/3XYcQQU

2. Goyal L, Meric-Bernstam F, Hollebecque A, et al. Futibatinib for FGFR2-rearranged intrahepatic cholangiocarcinoma. N Engl J Med. 2023; 388:228-239. doi:10.1056/NEJMoa2206834