FOENIX-CCA2: A phase II, open-label, multicenter study of futibatinib in patients (pts) with intrahepatic cholangiocarcinoma (iCCA) harboring <i>FGFR2</i> gene fusions or other rearrangements.

108 Background: Patients (pts) with intrahepatic cholangiocarcinoma (iCCA) have a 5-year survival rate of 24%. There is no standard treatment for advanced disease after first-line chemotherapy. Fibroblast growth factor receptor-2 ( FGFR2) gene fusions occur in 10% to 20% of pts with iCCA, offering a promising therapeutic avenue for this disease. Futibatinib is a highly selective irreversible FGFR1-4 inhibitor given as a continuous once-daily (QD) oral regimen. This phase 2 registrational trial was initiated because of results from a phase 1 dose escalation/expansion study showing tolerability and preliminary efficacy of futibatinib in pts with iCCA with FGFR2 fusions. Methods: FOENIX-CCA2 (NCT02052778), a single-arm multicenter phase 2 study, enrolled pts with locally advanced/metastatic unresectable iCCA harboring FGFR2 gene fusions or other rearrangements, disease progression after ≥1 line of systemic therapy (including gemcitabine plus platinum-based chemotherapy), no prior FGFR inhibitor treatment, and an ECOG performance status of 0 or 1. Pts received futibatinib 20 mg QD until disease progression/unacceptable toxicity. The primary endpoint is objective response rate (ORR) based on independent central radiology review. Secondary endpoints include disease control rate (DCR), duration of response (DOR), and safety. Results: A total of 103 pts were enrolled. For this interim analysis, data are reported for the 67 pts (65%) with ≥6 months of follow-up. Of these, 82.1% of pts had tumors harboring an FGFR2 fusion. One, 2, or ≥3 prior therapies were received by 44.8%, 28.4%, and 26.9% of pts, respectively. ORR was 34.3% (all partial response, n = 23), and DCR was 76.1%; assessment was pending for 8 pts. Median time to response was 1.6 months (range, 1.0-4.9), and median DOR was 6.2 months (range, 2.1-14.2). The most common treatment-related adverse events (AEs; all grade, grade ≥3) were hyperphosphatemia (79.1%, 25.4%), diarrhea (37.3%, 0%), and dry mouth (32.8%, 0%). Any-cause grade ≥3 AEs were reported in 73.1% of pts. Dose delay or dose reduction was required in 65.7% and 53.7% of pts, respectively; 6.0% of pts discontinued treatment because of AEs. Conclusions: Preliminary assessment of these phase 2 data indicate efficacy and tolerability of futibatinib for treatment of pts with iCCA harboring FGFR2 fusions or other rearrangements who have progressed after chemotherapy. Continued analysis of the study population is underway. Clinical trial information: NCT02052778.