A phase II telemedicine study of pemigatinib in adult patients with unresectable or metastatic pancreas cancer with FGFR2 gene fusions or other FGFR genetic alterations.
Authors: Risch Zachary , Wing Michele , Reeser Julie , Stein Leah , Dao Thuy , Smith Amy , Samorodnitsky Eric , Paruchuri Anoosha , Pan Xueliang Jeff , Roychowdhury Sameek 
Published: January 2024

TPS717 Background: Advanced pancreas cancer has a poor prognosis with few effective targeted therapies. Given this current state, novel therapies for pancreas cancer are an unmet need. Genomic alterations in FGFR, including fusions and point mutations are known driver mutations in cancer. FGFR kinase inhibitors have been FDA approved in cholangiocarcinoma and urothelial carcinoma, however, have not been well studied in other cancers. Our team previously identified and treated four patients with advanced pancreas cancer and FGFR2 fusions with FGFR kinase inhibitors resulting in durable responses and prolonged survival. Additionally, through a review of Foundation Medicine’s clinical genomic database, consisting of 30,229 pancreas cancer tumors, we determined that FGFR1-3 fusions have a prevalence of approximately 1% in pancreas cancer, most commonly in FGFR2 (0.8%). Our observations provide preliminary evidence that FGFR targeted therapy results in excellent clinical outcomes. We hypothesize that FGFR altered pancreas cancer treated with a FGFR kinase inhibitor will result in durable responses. We developed a phase 2, telemedicine trial of pemigatinib, an FDA approved FGFR kinase inhibitor, in FGFR altered pancreas cancer. Since the COVID-19 pandemic, telemedicine is used in routine oncology care and clinical trials and is associated with cost savings for patients. The growing adoption of this technology provides an opportunity to enhance the study of ultra-rare cancers. Methods: The trial consists of unresectable or metastatic pancreas cancer of any histology in two cohorts: 1) Primary cohort of FGFR2 fusions (n=30) and 2) exploratory cohort of other known activating mutations in FGFR (n=10). Patients are identified from across the United States through Foundation Medicine, Caris Life Sciences, and the Pancreatic Cancer Action Network. Eligible patients will be treated with oral pemigatinib through telemedicine by investigators at The Ohio State University in collaboration with local oncologists for supportive care. This trial uses single-stage phase 2 design with sample size calculations based on an expected overall response rate of ≥ 33% and <10% as unfavorable response, at one‐sided Type I error of 0.05, 90% power and up to 13% attrition rate. Results: The primary objective is overall response rate. Secondary objectives are overall survival, progression free survival, and duration of response. Exploratory objectives are analysis of correlation of circulating tumor DNA with response to treatment and development of resistance. Conclusions: FGFR kinase inhibitorshave the potential to be an effective targeted therapy in pancreas cancer. Additionally, telemedicine is a novel tool that can aid in the study of ultra-rare cancers and reduce barriers to patient participation in clinical trials.