FDA Grants Accelerated Approval to Futibatinib in FGFR2+ Locally Advanced/Metastatic Intrahepatic Cholangiocarcinoma


Results from the phase 1/2 TAS-120-101 trial lead to the accelerated approval of futibatinib in patients with locally advanced or metastatic cholangiocarcinoma and an FGFR2 gene fusion or rearrangement.

The FDA has granted accelerate approval to futibatinib (Lytgobi) for patients with previously treated unresectable, locally advanced or metastatic cholangiocarcinoma whose tumors harbor a FGFR2 gene rearrangement or fusion, according to a press release from the FDA.1

The approval was based on results of the multicenter, open-label, single-arm phase 1/2 TAS-120-101 trial (NCT02052778) in which the irreversible inhibitor of FGFR1/2/3/4 was used to treat 103 patients of this subset. The objective response rate (ORR) by independent review committee was 42% (95% CI, 32%-52%) with all 43 patients achieving a partial response as their best response. The median duration of response (DOR) was 9.7 months (95% CI, 7.6-17.1).

“Lytgobi is a key example of the potential of precision medicine in [intrahepatic cholangiocarcinoma] and represents another advance in the treatment of this rare and challenging disease,” Lipika Goyal, MD, MPhil, of the Massachusetts General Hospital Cancer Center and lead investigator of the pivotal TAS-120-101 trial, said in a statement. “I am encouraged that treatment options continue to expand and evolve for this disease through the dedicated efforts of many over several years.”

Another trial examining the agent in the indicated patient population was the phase 2b FOENIX-CCA2 trial (NCT02052778), for which updated findings were presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting.2 A total of 103 patients with advanced or metastatic FGFR2-altered intrahepatic cholangiocarcinoma were enrolled and received 20 mg of oral futibatinib once daily continuously for 21-day cycles. Treatment continued until disease progression, drug intolerance, withdrawal of consent, or death. Patients could have a maximum of 2 dose reductions to 16 mg then to 12 mg to mitigate adverse effects (AEs).

The primary end point was ORR, with secondary end points including DOR, disease control rate (DCR), progression-free survival (PFS), overall survival (OS), safety, and patient-reported outcomes.

The median follow-up was 25.0 months and 93% of patients had discontinued treatment by final data cutoff. The median number of treatment cycles was 13.0 with a median treatment duration of 9.1 months.

Median age was 58 years, 56% of patients were female, and 53% had an ECOG performance status of 1. FGFR2 fusions were observed in 78% of patients and 22% had a rearrangement. Prior anticancer therapy was administered in all patients, with 27% receiving prior radiotherapy. The majority of patients (47%) had at least 1 prior systemic therapy, and the median time from prior anticancer therapy to the first futibatinib dose was 1.5 months.

The ORR was 41.7% (95% CI, 32.1%-51.9%), and the DCR was 82.5% (95% CI, 73.8%-89.3%). A complete response was observed in 1 patients, 42 had a partial response, 42 had stable disease, and 16 had progressive disease. The median DOR was 9.5 months (95% CI, 7.6-10.4) and the median time to response was 2.6 months (95% CI, 0.7-15.4). In the pre-specified subgroup analysis, the ORR was consistent across patient all subgroups.

The median PFS was 8.9 months (95% CI, 6.7-11.0). At 6 months the PFS rate was 65%, and at 12 months it was 35%. The median OS was 20.0 months (95% CI, 16.4-24.6). The PFS rate at 6 months was 88% and at 12 months it was 73%.

The most common treatment-related AEs (TRAEs) of any grade included hyperphosphatemia, alopecia, dry mouth, and diarrhea. Most TRAEs were grade 3 or less, but there were 2 grade 4 events. Grade 3AEs of special interest included hyperphosphatemia (31%), increased alanine transaminase and aspartate transaminase (12%), Palmar-plantar erythrodysesthesia syndrome (6%), and nail toxicities (2%).

Patient-reported outcomes showed quality of life was maintained from baseline to treatment cycle 13. There was a mean change from baseline of –8.9 in 44 patients at the end of treatment.


  1. FDA grants accelerated approval to futibatinib for cholangiocarcinoma. News release. FDA. September 30, 2022. Accessed September 30, 2022. https://bit.ly/3BQZwnG
  2. Goyal L, Meric-Bernstam F, Hollebecque A, et al. Updated results of the FOENIX-CCA2 trial: Efficacy and safety of futibatinib in intrahepatic cholangiocarcinoma (iCCA) harboring FGFR2 fusions/rearrangements. J Clin Oncol. 2022;40(suppl 16):4009. doi:10.1200/JCO.2022.40.16_suppl.4009

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