P-113 FIGHT-302: Phase 3 study of first-line pemigatinib vs gemcitabine + cisplatin for cholangiocarcinoma with FGFR2 fusions or rearrangement

For advanced cholangiocarcinoma, standard-of-care first-line systemic treatment is gemcitabine + cisplatin. Activating genetic alterations in patients with intrahepatic cholangiocarcinoma provide potential therapeutic targets. Fibroblast growth factor receptor (FGFR) 2 gene fusions or rearrangements drive cholangiocarcinoma tumorigenesis and occur in 10–16% of patients, being almost exclusively confined to patients with intrahepatic cholangiocarcinoma. In phase 2, pemigatinib (INCB054828), a selective, potent, oral FGFR1–3 inhibitor elicited an objective response rate (ORR) of 35.5%, a median progression-free survival (PFS) of 6.9 months, a median duration of response (DOR) of 9.1 months, and a disease control rate (DCR) of 82.0% in previously treated, locally advanced, or metastatic cholangiocarcinoma with FGFR2 rearrangements (FIGHT-202; NCT02924376). FIGHT-302, a randomized, open-label, phase 3 study, will evaluate efficacy and safety of first-line pemigatinib vs gemcitabine + cisplatin in unresectable/metastatic cholangiocarcinoma with documented FGFR2 fusions or rearrangements (NCT03656536). Eligible patients are adults who have confirmed, radiographically measurable/evaluable (per Response Evaluation Criteria in Solid Tumors [RECIST] v1.1) unresectable/metastatic cholangiocarcinoma with documented FGFR2 fusions or rearrangements, received no prior systemic therapy for advanced disease 5.5 mg/dL) or grade ≥2 treatment-related adverse events (cycle 1). Hyperphosphatemia will be managed with diet modifications, phosphate binders, diuretics, or dose adjustments. Treatment will continue until disease progression or unacceptable toxicity. Primary endpoint is PFS (independent review). Secondary endpoints are ORR, overall survival (OS), DOR, DCR, safety, and quality of life. Exploratory endpoints include evaluation of the relationship between specific FGFR2 alterations and clinical activity (assessed by their association with PFS, OS and ORR), and the relationship between biomarkers and clinical activity that may be indicative of clinical response, safety, pharmacodynamics and/or pemigatinib mechanism of action. Sites are open across US, Europe and Asia. NCT03656536. Incyte Corporation. Incyte Corporation.