Abstract CT059: Phase 2, open-label, multicenter study of the efficacy and safety of INCB054828 for metastatic or surgically unresectable urothelial carcinoma harboring fibroblast growth factor (FGF)/FGF receptor (FGFR) alterations
Authors: Shore Neal D. , Asatiani Ekaterine , Lihou Christine F. , Zhen Huiling , Gupta Sumati 
Published: July 2017

Abstract
Background: Aberrant FGFR signaling results in tumor cell proliferation, migration, and survival, as well as angiogenesis, and is implicated in the development and progression of many cancers, including urothelial carcinoma (UC). Ten to 15% of patients with advanced UC have FGFR3 mutations and 6% have an FGFR3 translocation. INCB054828 is a novel, selective, orally administered inhibitor of FGFR1, FGFR2, and FGFR3 tyrosine kinase activities (AACR 2015; Abstract 771).
Methods: This phase 2, open-label trial will evaluate INCB054828 monotherapy for histologically confirmed metastatic or unresectable UC (NCT02872714; Table). Eligible patients will have known FGF/FGFR alterations, will be ≥18 years of age, have Eastern Cooperative Oncology Group performance status ≤2, adequate liver and renal function, and have life expectancy ≥12 wks. Patients will have inadequate response to ≥1 previous treatment in this setting or will be platinum-ineligible, and must not have received any investigational drugs within 21 days of first dose, including selective FGFR inhibitors. Patients will self-administer INCB054828 orally once daily at a starting dose of 13.5 mg on a 21-day 2-weeks-on and 1-week-off cycle. Patients will receive treatment until disease progression or unacceptable toxicity. The primary endpoint will be objective response rate (complete plus partial responses assessed from CT scans [or MRI per investigator] using Response Evaluation Criteria in Solid Tumors v1.1). Secondary endpoints will include safety, duration of response, progression-free survival, and overall survival. Exploratory endpoints will include predictive biomarker assessment. The study is currently recruiting; 96 patients are planned for the primary analysis (estimated to occur in March 2018).
Study DesignPrescreen for FGF/FGFR Status• Adults with metastatic/surgically unresectable urothelial carcinoma with inadequate response to ≥1 previous treatment or platinum-ineligible- Positive for FGF/FGFR alterations → continue screening- Negative for FGF/FGFR alterations → discontinue studyScreen for eligibility criteria and patient characteristics• Eastern Cooperative Oncology Group performance status ≤2• Adequate hepatic function (total bilirubin ≤1.5 × upper limit of normal [ULN; ≤2.5 × ULN for Gilbert syndrome or liver metastasis]; aminotransferases &lt;2.5 × ULN [&lt;5 × ULN for liver metastases])• Adequate renal function (creatinine clearance ≥30 mL/min; serum phosphate &gt;institutional ULN; serum calcium &gt;institutional normal range)• Life expectancy ≥12 weeksEnroll and start INCB054828 treatment• Oral once daily dosing: 21-day (2-weeks-on/1-week-off) cycleStart clinical assessment after cycle 3• Stable disease/partial or complete response → continue treatment on 21-day cycle; clinical assessments every 3 cycles• Disease progression → discontinue treatment; safety and survival follow-up
Citation Format: Neal D. Shore, Ekaterine Asatiani, Christine F. Lihou, Huiling Zhen, Sumati Gupta. Phase 2, open-label, multicenter study of the efficacy and safety of INCB054828 for metastatic or surgically unresectable urothelial carcinoma harboring fibroblast growth factor (FGF)/FGF receptor (FGFR) alterations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr CT059. doi:10.1158/1538-7445.AM2017-CT059