Abstract CT063: Phase 2, open-label, multicenter study of the efficacy and safety of INCB054828 in patients (pts) with advanced, metastatic, or surgically unresectable cholangiocarcinoma (CCA) with inadequate response to prior therapy
Authors: Borad Mitesh J. , Davis S. Lindsey , Lowery Maeve A. , Asatiani Ekaterine , Lihou Christine F. , Zhen Huiling , Abou-Alfa Ghassan K. 
Published: July 2017

Abstract
Background: Dysregulation of fibroblast growth factor receptor (FGFR) signaling by FGFR translocations and activating mutations is implicated in many cancers, including CCA. FGFR2 translocations are the most common FGFR alterations, which occur in ~13% of pts with intrahepatic CCA and involve a variety of fusion partners/breakpoints. INCB054828 is a novel, orally available, selective inhibitor of FGFR1, FGFR2, and FGFR3 tyrosine kinase activities (AACR 2015; Abstract 771).
Methods: This phase 2, open-label trial will evaluate INCB054828 monotherapy in pts with advanced/metastatic or surgically unresectable CCA (Table; NCT02924376). Pts will be prescreened centrally for FGF/FGFR status and enrolled in the following cohorts prior to start of treatment: FGFR2 translocations (Cohort A); other FGF/FGFR alterations (Cohort B); no FGF/FGFR alterations (Cohort C; negative control for effects of FGF/FGFR alterations on objective response rate [ORR]). Pts must be aged ≥18 years, with Eastern Cooperative Oncology Group performance status ≤2, disease progression after ≥1 prior systemic therapy, and no prior use of selective FGFR inhibitors. Pts will self-administer INCB054828 orally at a starting dose of 13.5 mg once-daily on a 21-day cycle (2 weeks on; 1 week off); treatment will continue until disease progression or unacceptable toxicity. The primary endpoint will be ORR (complete or partial response per independent radiologic review committee using Response Evaluation Criteria in Solid Tumors v1.1) in pts with FGFR2 translocations (Cohort A). Secondary endpoints will include ORR in pts positive or negative for any FGF/FGFR alterations and duration of response, progression-free survival, overall survival, and safety (all cohorts). The study is currently open for enrollment (estimated primary completion date, April, 2018).
Study DesignPrescreen for FGF/FGFR Status• Adults with metastatic/surgically unresectable cholangiocarcinoma with disease progression after ≥1 previous systemic treatment- FGFR2 translocations → cohort A (n~60)- Other FGF/FGFR alterations → cohort B (n~20)- No FGF/FGFR alterations → cohort C (n~20)Screen 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 disease involving liver]; aminotransferases &lt;2.5 × ULN [&lt;5 × ULN with liver metastases])• Adequate renal function (creatinine clearance ≥30 mL/min; serum phosphate &gt;institutional ULN; serum calcium &gt;institutional normal range; potassium &gt;institutional lower limit of normal)• Life expectancy ≥12 weeksEnroll and initiate INCB054828 treatment• Oral once daily dosing: 21-day (2-weeks-on/1-week-off) cycleStart response assessment after cycle 2• Stable disease/partial or complete response → continue treatment with restaging after cycle 4; imaging assessments increase to every 3 cycles after cycle 4• Disease progression → discontinue treatment; safety and survival follow-up
Citation Format: Mitesh J. Borad, S. Lindsey Davis, Maeve A. Lowery, Ekaterine Asatiani, Christine F. Lihou, Huiling Zhen, Ghassan K. Abou-Alfa. Phase 2, open-label, multicenter study of the efficacy and safety of INCB054828 in patients (pts) with advanced, metastatic, or surgically unresectable cholangiocarcinoma (CCA) with inadequate response to prior therapy [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 CT063. doi:10.1158/1538-7445.AM2017-CT063