FIGHT-302: Phase 3 study of first-line pemigatinib vs gemcitabine plus cisplatin for cholangiocarcinoma with FGFR2 fusions or rearrangement

Abstract

Background:For advanced cholangiocarcinoma, standard-of-carefirst-line systemictreatment is gemcitabine + cisplatin. Activating genetic alterations in patients withintrahepatic cholangiocarcinoma provide potential therapeutic targets. Fibroblastgrowth factor receptor (FGFR) 2 gene fusions or rearrangements drive chol-angiocarcinoma tumorigenesis and occur in 10e16% of patients, being almostexclusively confined to patients with intrahepatic cholangiocarcinoma. In phase 2,pemigatinib (INCB054828), a selective, potent, oral FGFR1e3 inhibitor elicited anobjective response rate (ORR) of 35.5%, a median progression-free survival (PFS) of6.9 months, a median duration of response (DOR) of 9.1 months, and a diseasecontrol rate (DCR) of 82.0% in previously treated, locally advanced, or metastaticcholangiocarcinoma with FGFR2 rearrangements (FIGHT-202; NCT02924376). FIGHT-302, a randomized, open-label, phase 3 study, will evaluate efficacy and safety offirst-line pemigatinib vs gemcitabine + cisplatin in unresectable/metastatic chol-angiocarcinoma with documented FGFR2 fusions or rearrangements (NCT03656536).Trial design:Eligible patients are adults who have confirmed, radiographicallymeasurable/evaluable (per Response Evaluation Criteria in Solid Tumors [RECIST]v1.1) unresectable/metastatic cholangiocarcinoma with documented FGFR2 fusionsor rearrangements, received no prior systemic therapy for advanced disease 5.5 mg/dL) or grade 2 treatment-related adverse events (cycle 1). Hyperphosphatemia willbe managed with diet modifications, phosphate binders, diuretics, or dose adjust-ments. Treatment will continue until disease progression or unacceptable toxicity.Primary endpoint is PFS (independent review). Secondary endpoints are ORR, overallsurvival (OS), DOR, DCR, safety, and quality of life. Exploratory endpoints includeevaluation of the relationship between specific FGFR2 alterations and clinical activity(assessed by their association with PFS, OS and ORR), and the relationship betweenbiomarkers and clinical activity that may be indicative of clinical response, safety,pharmacodynamics and/or pemigatinib mechanism of action. Sites are open acrossUS, Europe and Asia.