Abstract 4413
Background
Cholangiocarcinoma is the most common biliary tract malignancy with an estimated incidence in Europe of 0.4–1.8/100,000 patients, and approximately 5,000–10,000 new cases annually in the USA. Treatment options are limited with a need to provide increased disease control, improved outcome, and targeted therapy that is less toxic than standard chemotherapy. The fibroblast growth factor receptor (FGFR) family plays an important role in cholangiocarcinoma, with FGFR2 gene fusions detected in about 15% of patients. Infigratinib is an ATP-competitive, FGFR1–3-selective oral tyrosine kinase inhibitor. Based on preliminary evidence of infigratinib efficacy in patients with relapsed/refractory cholangiocarcinoma with FGFR2 fusions/translocations (phase 2 study CBJG398X2204), the PROOF trial is evaluating infigratinib versus gemcitabine + isplatin in front-line patients with advanced cholangiocarcinoma with FGFR2 gene fusions/translocations.
Trial design
Patients with advanced/metastatic or inoperable cholangiocarcinoma are randomized 1:1 to oral infigratinib once daily for 21 days of a 28-day treatment cycle versus intravenous gemcitabine (1000 mg/m2) plus cisplatin (25 mg/m2) on days 1&8 of a 21-day cycle. Treatment will continue until confirmed progressive disease by central review, intolerance, withdrawal of informed consent, or death. After 8 cycles of gemcitabine plus cisplatin, patients can continue treatment if the investigator considers that they are deriving continued benefit. Patients on the gemcitabine plus cisplatin arm who progress can cross-over to 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, PK and exploratory genetic alterations/biomarkers will also be measured. The study was initiated in February 2019 with planned enrollment of 350 patients with confirmed FGFR2 gene fusions/translocations.
Clinical trial identification
NCT03773302.
Editorial acknowledgement
Lee Miller; Miller Medical Communications Ltd.
Legal entity responsible for the study
QED Therapeutics.
Funding
QED Therapeutics.
Disclosure
G.K. Abou-Alfa: Advisory / Consultancy, Research grant / Funding (institution): QED Therapeutics; Advisory / Consultancy: Celsion; Advisory / Consultancy, Research grant / Funding (institution): Celgene; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Sillajen; Advisory / Consultancy: Boston Scientific; Advisory / Consultancy: SERVIER; Advisory / Consultancy, Research grant / Funding (institution): Agios; Advisory / Consultancy: ASLAN Pharmaceuticals; Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy: Delcath Systems; Advisory / Consultancy: Eisai; Advisory / Consultancy, Research grant / Funding (institution): Halozyme; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Merck Serono; Advisory / Consultancy: Sirtex Medical; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Medimmune; Advisory / Consultancy: Amgen; Advisory / Consultancy: Antengene; Advisory / Consultancy: Astellas; Advisory / Consultancy: Aptus Clinical; Advisory / Consultancy: Carsgen Therapeutics; Advisory / Consultancy, Research grant / Funding (institution): CASI Pharmaceuticals; Advisory / Consultancy: Onxeo; Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy, Research grant / Funding (institution): Exelixis; Advisory / Consultancy: Daiichi Sankyo; Advisory / Consultancy: Debiopharm Group; Advisory / Consultancy: Inovio Pharmaceuticals; Advisory / Consultancy: PCI Biotech; Advisory / Consultancy: Yakult Pharmaceutical; Advisory / Consultancy: 3DMedcare; Advisory / Consultancy: Alignmed; Advisory / Consultancy, Research grant / Funding (institution): BeiGene; Advisory / Consultancy: BridgeBio Pharma; Advisory / Consultancy: Cipla; Advisory / Consultancy: Genoscience Pharma; Advisory / Consultancy: Hengrui Pharmaceutical; Advisory / Consultancy: Jazz Pharmaceuticals; Advisory / Consultancy: Kyowa Hakko Kirin; Advisory / Consultancy: LAM Therapeutics; Advisory / Consultancy, Research grant / Funding (institution): Lilly; Advisory / Consultancy: Minapharma; Advisory / Consultancy: Novella Clinical; Advisory / Consultancy: RedHill Biopharma; Advisory / Consultancy: Tekmira; Advisory / Consultancy: twoXAR; Advisory / Consultancy: Yiviva; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): Incyte; Research grant / Funding (institution): MabVax; Research grant / Funding (institution): Momenta Pharmaceuticals; Research grant / Funding (institution): OncoMed; Research grant / Funding (institution): Array BioPharma; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Acta Biologica; Research grant / Funding (institution), Travel / Accommodation / Expenses: Polaris; Research grant / Funding (institution): OncoQuest; Research grant / Funding (institution): Puma Biotechnology; Spouse / Financial dependant: Silenseed; Spouse / Financial dependant: EMD Serono; Spouse / Financial dependant: Gilead Sciences; Spouse / Financial dependant: Vicus Therapeutics; Spouse / Financial dependant: CytomX Therapeutics; Spouse / Financial dependant: BiolineRx; Spouse / Financial dependant: Janssen; Spouse / Financial dependant: Loxo; Spouse / Financial dependant: Newlink Genetics; Spouse / Financial dependant: Pfizer; Spouse / Financial dependant: Pharmacyte Biotech; Spouse / Financial dependant: Pharmacyclics; Spouse / Financial dependant: Pieris Pharmaceuticals; Spouse / Financial dependant: SOBI; Spouse / Financial dependant: Targovax. I. Borbath: Advisory / Consultancy, Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Ipsen; Research grant / Funding (institution): Celgene. S.J. Clarke: Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck; Advisory / Consultancy, Speaker Bureau / Expert testimony: Ipsen; Advisory / Consultancy: Bayer; Advisory / Consultancy: AstraZeneca/MedImmune; Speaker Bureau / Expert testimony: Novartis. C. Louvet: Honoraria (self), Travel / Accommodation / Expenses: Roche; Honoraria (self), Travel / Accommodation / Expenses: MSD; Honoraria (self): Halozyme; Honoraria (self): Servier. D. Oh: Advisory / Consultancy, Research grant / Funding (self): AstraZeneca; Advisory / Consultancy, Research grant / Funding (self): Novartis; Advisory / Consultancy: Genentech/Roche; Advisory / Consultancy: Merck Serono; Advisory / Consultancy: Bayer; Advisory / Consultancy: Taiho Pharmaceutical; Advisory / Consultancy: ASLAN Pharmaceuticals; Research grant / Funding (self): Array BioPharma; Research grant / Funding (self): Lilly; Research grant / Funding (self): Green Cross. J.L. Spratlin: Honoraria (self), Advisory / Consultancy: Celgene; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Sanofi; Honoraria (self), Advisory / Consultancy: Lilly/ImClone; Advisory / Consultancy: Taiho Pharmaceutical; Advisory / Consultancy, Travel / Accommodation / Expenses: Astellas. J.W. Valle: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Ipsen; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Novartis; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Merck; Advisory / Consultancy: Delcath Systems; Advisory / Consultancy: Agios; Advisory / Consultancy: Pfizer; Advisory / Consultancy: PCI Biotech; Advisory / Consultancy: Incyte; Advisory / Consultancy: Keocyt; Advisory / Consultancy: QED Therapeutics; Advisory / Consultancy: Pieris Pharmaceuticals; Advisory / Consultancy: Genoscience Pharma; Advisory / Consultancy: Mundipharma EDO; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Nucana; Speaker Bureau / Expert testimony: Imaging Equipment Limited; Travel / Accommodation / Expenses: Celgene. K.H. Weiss: Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony: BMS; Advisory / Consultancy: Bayer; Advisory / Consultancy, Research grant / Funding (institution): Wilson Therapeutics; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): GMPO; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Univar; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Alexion Pharmaceuticals; Advisory / Consultancy, Research grant / Funding (institution): Eisai; Advisory / Consultancy: Chiesi; Advisory / Consultancy: Vivet Therapeutics; Speaker Bureau / Expert testimony: Falk Pharma; Speaker Bureau / Expert testimony: Ipsen; Licensing / Royalties: Gilead Sciences. C. Berman: Full / Part-time employment: QED Therapeutics. M. Howland: Full / Part-time employment: QED Therapeutics. Y. Ye: Full / Part-time employment: QED Therapeutics. T. Cho: Full / Part-time employment: QED Therapeutics. S. Moran: Full / Part-time employment: QED Therapeutics. All other authors have declared no conflicts of interest.
Resources from the same session
3006 - Nal-iri/lv5-fu versus paclitaxel as second-line therapy in patients with metastatic esophageal squamous cell carcinoma (OESIRI-PRODIGE 62): A FFCD multicenter, randomized, phase II study.
Presenter: Violaine Randrian
Session: Poster Display session 2
Resources:
Abstract
3697 - The expression of Versican and its role in pancreatic neuroendocrine tumor
Presenter: Zhao Sun
Session: Poster Display session 2
Resources:
Abstract
6073 - Characteristics of patients with thyroid carcinoma in the united states
Presenter: Dina El-Habashy
Session: Poster Display session 2
Resources:
Abstract
2124 - The discrimination of pituitary adenomas and craniopharyngioma on MRI: from image features to texture features
Presenter: Hanyue Xu
Session: Poster Display session 2
Resources:
Abstract
3786 - Proportion of Peripheral Lymphocyte Subsets Correlates with the Progression-free Survival and Metastatic Status of Pancreatic Neuroendocrine Tumor Patients
Presenter: Yitao Gong
Session: Poster Display session 2
Resources:
Abstract
2263 - Immunohistochemical expression of ER-α and PR in papillary thyroid carcinoma
Presenter: Enas Elkhouly
Session: Poster Display session 2
Resources:
Abstract
4386 - SILVELUL Project: Immunohistochemical panel analyses as potential predictive and prognostic factors in Pancreatic Neuroendocrine Tumors (PanNET) Treated with CAPTEM or Everolimus
Presenter: Ana De Jesus-Acosta
Session: Poster Display session 2
Resources:
Abstract
2302 - Carcinoid heart disease (CHD): the CRUSOE-NETs, a prospective cohort study from the French Group of Endocrine Tumors (GTE)
Presenter: Kathleen Dekeister Geoffroy
Session: Poster Display session 2
Resources:
Abstract
5749 - Safety of high doses of somatostatin analogs in well differentiated NENs in elderly
Presenter: Massimiliano Cani
Session: Poster Display session 2
Resources:
Abstract
3931 - Differences in multikinase inhibitors (MKI) toxicity profile according to gender. A pooled analysis of three phase II trials with lenvatinib, pazopanib and sorafenib in patients (pts) with advanced gastroenteropancreatic (GEP) neuroendocrine tumors (NETs).
Presenter: Jorge Hernando Cubero
Session: Poster Display session 2
Resources:
Abstract