FOENIX-CCA4: A phase 2 study of futibatinib 20 mg and 16 mg in patients with advanced cholangiocarcinoma (CCA) and fibroblast growth factor receptor 2 (FGFR2) fusions/rearrangements.

TPS572 Background: In 2022, the U.S. FDA approved futibatinib, a covalently binding inhibitor of FGFR1–4, for previously treated patients with advanced intrahepatic CCA and FGFR2 fusions/rearrangements. In the pivotal phase 2 FOENIX-CCA2 study, futibatinib 20 mg once daily (QD) resulted in an objective response rate (ORR) of 42% by independent review and a median duration of response (DOR) of 9.7 months. Futibatinib was tolerable and had a manageable safety profile. 1 Limited phase 1 data suggest futibatinib may also have antitumor activity at a lower dose (16 mg QD), with fewer dose modifications required for adverse events. 2 The aim of FOENIX-CCA4is to confirm the clinical benefit of futibatinib 20 mg QD and explore the safety and efficacy of futibatinib 16 mg QD in previously treated patients with advanced CCA and FGFR2 fusions/rearrangements. Methods: In this global, phase 2, randomized, open-label study (NCT05727176), patients with CCA harboring FGFR2 fusions/rearrangements who have received ≥1 line of gemcitabine/platinum-based therapy for advanced/metastatic disease will be randomized 1:1 to futibatinib at a starting dose of 20 mg or 16 mg QD continuously on a 21-day cycle. Randomization will be stratified by the number of prior lines of systemic therapy for advanced disease (1 vs ≥2). Futibatinib will be continued until progressive disease or unacceptable toxicity. Tumor response will be assessed at baseline, every 6 weeks for the first 12 weeks, and every 9 weeks thereafter until radiographic progressive disease or initiation of new anticancer therapy. The primary endpoint is ORR according to Response Evaluation Criteria in Solid Tumors version 1.1, as assessed by blinded independent central review (analyzed when all patients responding to futibatinib have ≥6 months’ follow-up from the first onset of response). DOR is a key secondary endpoint. Other secondary endpoints are progression-free survival, overall survival, safety, and quality of life. Sample size (120 patients) was estimated on the assumption that if the lower ORR between futibatinib 16 mg and 20 mg is 32% (with ≥60 patients per arm), the probability of correctly selecting the treatment arm with a true ORR of 42% is 0.87. Enrollment is ongoing in Europe, the US, and Asia-Pacific. 1. Goyal L et al. N Engl J Med. 2023;388:228–39. 2. Meric-Bernstam F et al. Cancer Discov. 2022;12:402–15. Clinical trial information: NCT05727176 .