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PROOF: A multicenter, open-label, randomized, phase III trial of infigratinib vs gemcitabine plus cisplatin in patients with advanced cholangiocarcinoma with FGFR2 gene rearrangements
Abou-Alfa, G. K. Borbath, I. Cohn, A. L. Goyal, L. Lamarca, Angela Macarulla, T. Oh, D. Y. Roychowdhury, S. Sadeghi, S. Shroff, R. T.
Abou-Alfa, G. K.
Borbath, I.
Cohn, A. L.
Goyal, L.
Lamarca, Angela
Macarulla, T.
Oh, D. Y.
Roychowdhury, S.
Sadeghi, S.
Shroff, R. T.
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Abstract
Background: Cholangiocarcinoma (CCA) treatment options are limited with a need to
provide better disease control, improved outcome, and targeted therapy that is less
toxic than standard chemotherapy. As the understanding of the molecular landscape
of CCA has increased, the fibroblast growth factor receptor (FGFR) family has been
found to play an important role in CCA. FGFR gene fusions and rearrangements
represent driver mutations; they are present in 13e17% of intrahepatic CCA and may
predict tumor sensitivity to FGFR inhibitors. Infigratinib (BGJ398) is an ATP-competitive,
FGFR1e3 selective oral tyrosine kinase inhibitor. Based on promising preliminary
response data of infigratinib in patients with relapsed/refractory CCA with FGFR2
gene fusions or other rearrangements (phase II trial CBJG398X2204), the PROOF trial
is evaluating infigratinib vs gemcitabine + cisplatin in front-line patients with
advanced CCA with FGFR2 gene rearrangements.
Trial design: Patients with advanced/metastatic or inoperable CCA with FGFR2 gene
fusions (determined by local or central laboratory) are randomized 2:1 to oral infigratinib
once daily for 21 days of a 28-day treatment cycle vs intravenous standard gemcitabine
(1000 mg/m2) + cisplatin (25 mg/m2) on days 1 and 8 of a 21-day cycle. Treatment will
continue until confirmed progressive disease by central review, intolerance, withdrawal
of informed consent, or death. Patients on the gemcitabine + cisplatin arm who develop
disease progression can cross-over to receive infigratinib. The primary endpoint is
progression-free survival (PFS, RECIST v1.1 central review). Secondary endpoints include
overall survival, PFS (investigator determined), overall response rate, disease control
rate, duration of response, and safety. Quality of life, pharmacokinetics and exploratory
genetic alterations/biomarkers will also be measured. The trial will have sites in the US,
EU, and APAC, including Australia. Enrollment is ongoing.
Description
Date
2020
Publisher
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Keywords
Type
Meetings and Proceedings
Citation
Abou-Alfa GK, Borbath I, Cohn AL, Goyal L, Lamarca A, Macarulla T, et al. 1014TiP PROOF: A multicenter, open-label, randomized, phase III trial of infigratinib vs gemcitabine + cisplatin in patients with advanced cholangiocarcinoma with FGFR2 gene rearrangements. Annals of Oncology. 2020;31:S701-S2.