Abstract 1014TiP
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 13–17% of intrahepatic CCA and may predict tumor sensitivity to FGFR inhibitors. Infigratinib (BGJ398) is an ATP-competitive, FGFR1–3 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.
Clinical trial identification
NCT03773302.
Editorial acknowledgement
Lee Miller (Miller Medical Communications).
Legal entity responsible for the study
QED Therapeutics Inc.
Funding
QED Therapeutics Inc.
Disclosure
G.K. Abou-Alfa: Advisory/Consultancy, Research grant/Funding (institution): Agios; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Bayer; Advisory/Consultancy, Research grant/Funding (institution): BeiGene; Advisory/Consultancy: BiolineRx; Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy, Research grant/Funding (institution): Celgene; Advisory/Consultancy: Debiopharm Group; Advisory/Consultancy: Eisai; Advisory/Consultancy, Research grant/Funding (institution): Exelixis; Advisory/Consultancy: Flatiron Health; Advisory/Consultancy: Genoscience Pharma; Advisory/Consultancy: Gilead Sciences; Advisory/Consultancy: Ipsen; Advisory/Consultancy: LAM Therapeutics; Advisory/Consultancy, Research grant/Funding (institution): Lilly; Advisory/Consultancy: Merck Serono; Advisory/Consultancy: Minapharma; Advisory/Consultancy, Research grant/Funding (institution): QED Therapeutics; Advisory/Consultancy: RedHill Biopharma; Advisory/Consultancy, Research grant/Funding (institution): Roche; Advisory/Consultancy: Sanofi; Advisory/Consultancy: Sillajen; Advisory/Consultancy: twoXAR; Advisory/Consultancy: Vicus Therapeutics; Advisory/Consultancy: Yiviva; Research grant/Funding (institution): Acta Biologica; Research grant/Funding (institution): Array BioPharma; Research grant/Funding (institution): CASI Pharmaceuticals; Research grant/Funding (institution): Genentech. I. Borbath: Advisory/Consultancy, Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Celgene; Research grant/Funding (institution): Ipsen. A. Lamarca: Honoraria (self), Travel/Accommodation/Expenses, educational support: Bayer; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses, Knowledge Network and NETConnect Initiatives funding: Ipsen; Honoraria (self), Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses, educational support: Pfizer; Advisory/Consultancy: Eisai; Advisory/Consultancy: Nutricia; Advisory/Consultancy: QED Therapeutics; Advisory/Consultancy: Roche; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: AAA; Speaker Bureau/Expert testimony: Incyte; Speaker Bureau/Expert testimony: Merck; Travel/Accommodation/Expenses: Delcath; Travel/Accommodation/Expenses: Mylan; Travel/Accommodation/Expenses: Novartis; Travel/Accommodation/Expenses: SirtExand. T. Macarulla: Advisory/Consultancy: Baxalta; Advisory/Consultancy: Baxter; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Celgene; Advisory/Consultancy: Incyte; Advisory/Consultancy: Ipsen; Advisory/Consultancy, Research grant/Funding (institution): Lilly; Advisory/Consultancy: QED Therapeutics; Advisory/Consultancy, Research grant/Funding (institution): Roche; Advisory/Consultancy, Travel/Accommodation/Expenses: Sanofi/Aventis; Advisory/Consultancy, Travel/Accommodation/Expenses: SERVIER; Advisory/Consultancy: Shire; Research grant/Funding (institution): Agios; Research grant/Funding (institution): ASLAN Pharmaceuticals; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): Halozyme; Research grant/Funding (institution): Immunomedics; Research grant/Funding (institution): Merrimack; Research grant/Funding (institution): Millennium; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Novocure; Research grant/Funding (institution): Pfizer S.L.U; Research grant/Funding (institution): Pharmacyclics; Travel/Accommodation/Expenses: H3 Biomedicine; Travel/Accommodation/Expenses: Merck. D-Y. Oh: Advisory/Consultancy: ASLAN; Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; Advisory/Consultancy: Bayer; Advisory/Consultancy: Celgene; Advisory/Consultancy: Genentech/Roche; Advisory/Consultancy: Halozyme; Advisory/Consultancy: Merck Serono; Advisory/Consultancy, Research grant/Funding (self): Novartis; Advisory/Consultancy: Taiho; Advisory/Consultancy: Zymeworks; Research grant/Funding (self): Array; Research grant/Funding (self): Eli Lilly. S. Roychowdhury: Honoraria (self): IDT Integrated DNA Technologies; Advisory/Consultancy: AbbVie, Inc; Advisory/Consultancy: Incyte Corporation; Advisory/Consultancy: QED Therapeutics. R.T. Shroff: Advisory/Consultancy: Agios; Advisory/Consultancy: Clovis; Advisory/Consultancy: Debiopharm; Advisory/Consultancy, Research grant/Funding (institution): Exelixis; Advisory/Consultancy: Incyte; Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy: QED Therapeutics; Advisory/Consultancy: Seattle Genetics; Research grant/Funding (institution): Haloyzme; Research grant/Funding (institution): Pieris; Research grant/Funding (institution): Rafael Pharmaceuticals; Research grant/Funding (institution): Taiho. M. Howland: Full/Part-time employment: QED Therapeutics Inc. A. Li: Full/Part-time employment: QED Therapeutics Inc. T. Cho: Full/Part-time employment: QED Therapeutics Inc. A. Pande: Full/Part-time employment: QED Therapeutics Inc. M. Javle: Advisory/Consultancy, Research grant/Funding (institution): Incyte; Advisory/Consultancy: Mundipharma EDO GmbH; Advisory/Consultancy: Oncosil; Advisory/Consultancy, Research grant/Funding (institution): QED Therapeutics; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): BeiGene; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Merck Serono; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Pieris Pharmaceuticals; Research grant/Funding (institution): Rafael Pharmaceuticals; Research grant/Funding (institution): Seattle Genetics. All other authors have declared no conflicts of interest.