Therapeutic efficacy of Futibatinib

TAS-120-101 (NCT02052778), a multicenter, open-label, single-arm trial, evaluated the efficacy of Futibatinib  in 103 patients with previously treated, unresectable, locally advanced or metastatic intrahepatic  cholangiocarcinoma.The presence of FGFR2 fusions or other rearrangements was determined in 102 enrolled  patients (99%) using next generation sequencing (NGS) testing. Qualifying in-frame fusions and other  rearrangements were predicted to have a breakpoint within intron 17/exon 18 of the FGFR2 gene leaving the  FGFR2 kinase domain intact.

Patients received Futibatinib at a dosage of 20 mg orally once daily until disease progression or unacceptable  toxicity. The major efficacy outcome measures were overall response rate (ORR) and duration of response  (DoR) as determined by an independent review committee (IRC) according to Response Evaluation Criteria in  Solid Tumors (RECIST) v1.1.

The trial population characteristics were: Median age was 58 years (range: 22 to 79 years) with 22% of patients  ≥65 years, 56% were female, race was: 50% White, 29% Asian, 8% Black or African American, 1% Native  Hawaiian or Other Pacific Islander, 13% unknown, baseline Eastern Cooperative Oncology Group (ECOG)  performance status of 0 (47%) or 1 (53%). Seventy-eight percent (78%) of patients had in-frame FGFR2 gene  fusions and the most commonly identified FGFR2 fusion partner was BICC1 (n=24, 23%). Twenty-two percent  (22%) of patients had other FGFR2 rearrangements that may not be in-frame with the partner gene or the  partner gene was not identifiable.

All patients had received at least 1 prior systemic therapy, 30% had 2 prior lines of therapy, and 23% had 3 or  more prior lines of therapy. All patients received a prior platinum-based therapy including 91% with prior  gemcitabine/cisplatin.

Efficacy results are summarized in Table 5. The median time to response was 2.5 months (range 0.7 – 7.4  months).

FDA，2022.09