Infigratinib in patients with advanced cholangiocarcinoma with FGFR2 gene fusions/translocations: the PROOF 301 trial

Shalini Makawita; Ghassan K Abou-Alfa; Sameek Roychowdhury; Saeed Sadeghi; Ivan Borbath; Lipika Goyal; Allen Cohn; Angela Lamarca; Do-Youn Oh; Teresa Macarulla; Rachna T Shroff; Michael Howland; Ai Li; Terry Cho; Amit Pande; Milind Javle

doi:10.2217/fon-2020-0299

Infigratinib in patients with advanced cholangiocarcinoma with FGFR2 gene fusions/translocations: the PROOF 301 trial

Future Oncol. 2020 Oct;16(30):2375-2384. doi: 10.2217/fon-2020-0299. Epub 2020 Jun 25.

Authors

Shalini Makawita¹, Ghassan K Abou-Alfa^{2

3}, Sameek Roychowdhury⁴, Saeed Sadeghi⁵, Ivan Borbath⁶, Lipika Goyal^{7

8}, Allen Cohn⁹, Angela Lamarca¹⁰, Do-Youn Oh¹¹, Teresa Macarulla¹², Rachna T Shroff¹³, Michael Howland¹⁴, Ai Li¹⁴, Terry Cho¹⁴, Amit Pande¹⁴, Milind Javle^{1

15}

Affiliations

¹ Division of Cancer Medicine, M.D. Anderson Cancer Center, Houston, TX 77030, USA.
² Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
³ Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA.
⁴ Division of Medical Oncology, Department of Internal Medicine, The James Cancer Hospital & Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
⁵ Department of Medicine, Division of Hematology/Oncology, University of California, Los Angeles, CA 90404, USA.
⁶ Department of Gastroenterology & Digestive Oncology, Cliniques Universitaires Saint-Luc & Université Catholique de Louvain, Brussels, Belgium.
⁷ Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
⁸ Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
⁹ Rocky Mountain Cancer Center & US Oncology Research, Denver, CO 80218, USA.
¹⁰ Department of Medical Oncology, The Christie NHS Foundation Trust, Division of Cancer Sciences, University of Manchester, Manchester, UK.
¹¹ Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea.
¹² Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology & IOB quirón, Barcelona, Spain.
¹³ Division of Hematology/Oncology, University of Arizona Cancer Center, Tucson, AZ 85724, USA.
¹⁴ QED Therapeutics, San Francisco, CA, USA.
¹⁵ Department of Gastrointestinal Medical Oncology, M.D. Anderson Cancer Center, Houston, TX 77030, USA.

PMID: 32580579
DOI: 10.2217/fon-2020-0299

Abstract

Cholangiocarcinoma is an aggressive malignancy with poor overall survival. Approximately 15% of intrahepatic cholangiocarcinomas contain FGFR alterations. Infigratinib is an oral FGFR 1-3 kinase inhibitor. Favorable results from a Phase II trial of infigratinib in advanced/metastatic FGFR-altered cholangiocarcinomas has led to its further investigation in the front-line setting. In this article we describe the design, objectives and rationale for PROOF 301, a Phase III multicenter, open label, randomized trial of infigratinib in comparison to standard of care gemcitabine and cisplatin in advanced/metastatic cholangiocarcinoma with FGFR2 translocations. The results of this study have the potential to define a new role for a chemotherapy-free, targeted therapy option in the front-line setting for these patients. Clinical Trial Registration: NCT03773302 (ClincalTrials.gov).

Keywords: cholangiocarcinoma; fibroblast growth factor receptor inhibitor; infigratinib; targeted therapy.

Publication types

Clinical Trial, Phase III
Multicenter Study
Randomized Controlled Trial

MeSH terms

Antineoplastic Combined Chemotherapy Protocols / adverse effects
Antineoplastic Combined Chemotherapy Protocols / therapeutic use
Bile Duct Neoplasms / drug therapy*
Bile Duct Neoplasms / genetics*
Bile Duct Neoplasms / pathology
Cholangiocarcinoma / drug therapy*
Cholangiocarcinoma / genetics*
Cholangiocarcinoma / pathology
Cisplatin / administration & dosage
Clinical Protocols*
Deoxycytidine / administration & dosage
Deoxycytidine / analogs & derivatives
Gemcitabine
Humans
Molecular Targeted Therapy
Mutation
Oncogene Proteins, Fusion / genetics*
Phenylurea Compounds / administration & dosage
Phenylurea Compounds / therapeutic use*
Protein Kinase Inhibitors / administration & dosage
Protein Kinase Inhibitors / therapeutic use
Pyrimidines / administration & dosage
Pyrimidines / therapeutic use*
Receptor, Fibroblast Growth Factor, Type 2 / antagonists & inhibitors
Receptor, Fibroblast Growth Factor, Type 2 / genetics*
Research Design
Translocation, Genetic

Substances

Oncogene Proteins, Fusion
Phenylurea Compounds
Protein Kinase Inhibitors
Pyrimidines
Deoxycytidine
infigratinib
FGFR2 protein, human
Receptor, Fibroblast Growth Factor, Type 2
Cisplatin
Gemcitabine

Associated data

ClinicalTrials.gov/NCT03773302