Abstract CT057: Phase 2, open-label, multicenter study to evaluate the efficacy and safety of INCB054828 in patients with myeloid/lymphoid neoplasms with fibroblast growth factor receptor 1 (FGFR1) rearrangement
Authors: Verstovsek Srdan , Rambaldi Alessandro , Asatiani Ekaterine , Lihou Christine F. , Zhen Huiling , Hochhaus Andreas 
Published: July 2017

Abstract
Background: Dysregulation of FGFR signaling is strongly implicated in the establishment and progression of many cancers; rearrangements in chromosome 8p11 leading to activation of FGFR1 have been associated with rare but aggressive myeloid and lymphoid neoplasms with eosinophilia. INCB054828 is a novel, selective, orally administered inhibitor of FGFR1, FGFR2, and FGFR3 tyrosine kinase activities (AACR 2015; Abstract 771).
Methods: This open-label, single-arm, phase 2 study will evaluate the efficacy and safety of INCB054828 monotherapy in patients with myeloid/lymphoid neoplasms with FGFR1 rearrangement (Table; NCT03011372). Eligible patients are ≥18 years of age, have documented lymphoid or myeloid neoplasm with 8p11 rearrangement known to lead to FGFR1 activation and have an Eastern Cooperative Oncology Group performance status ≤2. In addition, patients must not be candidates for stem cell transplant (or must have relapsed after transplant and delayed lymphocyte infusion); must have progressed on ≥1 prior anticancer treatment; must not be eligible for other disease-modifying therapies. Patients will self-administer INCB054828 orally, once-daily at a starting dose of 13.5 mg on a 21-day cycle (2 wks on; 1 wk off); treatment will continue until disease progression or unacceptable toxicity occurs. The primary endpoint will be overall clinical benefit rate (proportion of patients with complete or partial response, complete hematologic response, cytogenetic response, marrow response [see Table for response criteria], or clinical benefit). Secondary endpoints will include duration of response/clinical benefit, progression-free survival, overall survival, and safety. The study is currently recruiting (planned enrollment, n~46); primary analysis is expected in January 2019.
Study DesignScreen for eligibility criteria and patient characteristics• Documented lymphoid/myeloid neoplasm with 8p11 rearrangement known to lead to FGFR1 activation• Not candidates for stem cell transplantation (or have relapsed after transplantation and delayed lymphocyte infusion); progression on ≥1 prior anticancer treatment; not suitable for other disease-modifying therapies• 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 disease involving liver])• Adequate renal function (creatinine clearance ≥30 mL/min; serum phosphate &gt;institutional ULN; serum calcium within institutional normal range)• Life expectancy ≥12 weeksEnroll and initiate INCB054828 treatment• Oral once daily dosing: 21-day (2-weeks-on/1-week-off) cycleStart disease assessment* after cycle 2• Stable disease/partial or complete response → continue treatment on 21-day cycle• Disease progression → discontinue treatment; safety and survival follow-up*Bone marrow (BM) aspirates every 3 cycles starting from cycle 2 day 1 until month 12; then every 12 cycles until month 24 for patients with confirmed complete cytogenetic response; then every 12 months until disease progression or end of treatment. Response criteria are:• Complete response (CR): presence of all the following (1) bone marrow: ≤5% myeloblasts; 0% lymphoblasts; (2) peripheral blood: WBC ≤10x109/L; Hgb ≥11 g/dL; ≥100×109/L platelets ≤450×109/L; neutrophils ≥1.0×109/L; blasts 0%; neutrophil precursors ≤2%; monocytes ≤1×109/L; eosinophils ≤0.5×109/L; (3) prior extramedullary disease completely resolved• Complete cytogenetic response (CCyR): no 8p11 translocations• Complete hematologic response (CHR): see (2) under CR• Complete marrow response (CMR): see (1) under CR
Citation Format: Srdan Verstovsek, Alessandro Rambaldi, Ekaterine Asatiani, Christine F. Lihou, Huiling Zhen, Andreas Hochhaus. Phase 2, open-label, multicenter study to evaluate the efficacy and safety of INCB054828 in patients with myeloid/lymphoid neoplasms with fibroblast growth factor receptor 1 (FGFR1) rearrangement [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 CT057. doi:10.1158/1538-7445.AM2017-CT057