FIGHT-302: Phase 3 study of first-line pemigatinib vs gemcitabine plus cisplatin for cholangiocarcinoma with FGFR2 fusions or rearrangement
Vogel, A. van Cutsem, E. Rimassa, L. Furuse, J. Ioka, T. Melisi, D. Macarulla, T. Bridgewater, J. Wasan, H. S.
Vogel, A.
van Cutsem, E.
Rimassa, L.
Furuse, J.
Ioka, T.
Melisi, D.
Macarulla, T.
Bridgewater, J.
Wasan, H. S.
Citations
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Abstract
Introduction: For advanced cholangiocarcinoma, standard-of-care firstline
systemic treatment is gemcitabine + cisplatin. Genetic alterations in
intrahepatic cholangiocarcinoma provide potential therapeutic targets.
Fibroblast growth factor receptor (FGFR) 2 gene rearrangements driving
cholangiocarcinoma tumorigenesis were identified almost exclusively in
patients with intrahepatic cholangiocarcinoma (incidence, 10-16%). In
phase 2, pemigatinib (INCB054828), a selective, potent, oral FGFR1-3
inhibitor elicited an objective response rate (ORR) of 35.5% and median
progression-free survival (PFS) of 6.9 months 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).
Methods: Eligible patients are adults who have confirmed, radiographically
measurable/evaluable (per RECIST v1.1) unresectable/metastatic
cholangiocarcinoma with documented FGFR2 fusions or rearrangements,
received no prior systemic therapy for advanced disease < 6 months before
enrollment, and have an ECOG PS ?1. Exclusion criteria include clinically
significant corneal/retinal disorder, untreated CNS metastases, history of
seizures, and history of calcium and phosphate homeostasis disorder or
systemic mineral imbalance with ectopic soft tissue calcification. Patients
are randomized (1:1; stratified by region and tumor burden) to pemigatinib
13.5 mg QD on a 21-day cycle or gemcitabine (1000 mg/m2) + cisplatin
(25 mg/m2) on day 1 and day 8 of 21-day cycles (max 8). Crossover to
pemigatinib is allowed after confirmed disease progression. Pemigatinib
titration to 18 mg from cycle 2 is allowed for patients without hyperphosphatemia
(serum phosphate >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, duration of response, disease control rate, safety,
and quality of life.
Affiliation
Description
Date
2020
Publisher
Collections
Keywords
Type
Meetings and Proceedings
Citation
Vogel A, Valle JW, van Cutsem E, Rimassa L, Furuse J, Ioka T, et al. FIGHT-302: Phase 3 study of first-line pemigatinib vs gemcitabine plus cisplatin for cholangiocarcinoma with FGFR2 fusions or rearrangement. Oncology Research and Treatment. 2020;43(SUPPL 4):122-