Abstract CT080: A phase II study of JNJ-42756493, a pan-FGFR tyrosine kinase inhibitor, in patients with metastatic or unresectable urothelial cancer (UC) harboring FGFR gene alterations
Authors: Siefker-Radtke Arlene O. , Mellado Begoña , Decaestecker Karel , Burke John M. , O’ Hagan Anne , Avadhani Anjali , Zhong Bob , Santiago-Walker Ademi , De Porre Peter , Brookman-May Sabine , Garcia-Donas Jesus 
Published: July 2016

Abstract
Background: Current treatment options for metastatic UC remain limited, and tolerability is a concern in many patients. Alterations in the fibroblast growth factor receptor (FGFR) pathway are implicated in development of non-muscle-invasive bladder cancer; FGFR3 mutations or FGFR translocations are present in ∼10-20% of patients with metastatic UC. Treatment with pan-FGFR (FGFR1-4) inhibitor JNJ-42756493 resulted in promising antitumor activity in a phase 1 trial in patients with advanced solid tumors, including 3 partial responses among 8 patients with UC (Tabernero J, et al. J Clin Oncol. 2015). Safety was manageable and as anticipated with a potent FGFR inhibitor. This phase 2 open-label study of JNJ-42756493 (NCT02365597) is being conducted to determine efficacy and safety of 2 different dose regimens in patients with metastatic or unresectable UC with specific FGFR translocations or mutations.
Methods: Eligible patients must have disease progression following chemotherapy for metastatic or surgically unresectable UC or relapse within 12 months of the last dose of neoadjuvant/adjuvant chemotherapy. There is no limit on number of prior lines of treatment. Prior immunotherapy (eg, programmed-death 1/death-ligand 1 inhibitor) is allowed. Enrollment of cisplatin-ineligible (chemotherapy naïve) pts is allowed. Patients must have measurable disease (Response Evaluation Criteria In Solid Tumors version 1.1); Eastern Cooperative Oncology Group performance status ? 2; and adequate bone marrow, liver, and kidney function (creatinine clearance ? 40 mL/min). Patients with uncontrolled cardiovascular disease or baseline phosphate persistently above the upper limit of normal are not eligible. Eligible patients are randomized to 1 of 2 oral dose regimens of JNJ-42756493 in a 28-day cycle: an intermittent (10 mg/day for 7 days followed by 7 days off drug) or a continuous (6 mg/day) regimen until a dose regimen is selected. Approximately 110 patients will be treated at the selected dose regimen. Primary end point is objective response rate; secondary end points include progression-free survival, duration of response, overall survival, safety, biomarker, and pharmacokinetic assessments. This trial is currently enrolling in 14 countries.
Citation Format: Arlene O. Siefker-Radtke, Begoña Mellado, Karel Decaestecker, John M. Burke, Anne O’ Hagan, Anjali Avadhani, Bob Zhong, Ademi Santiago-Walker, Peter De Porre, Sabine Brookman-May, Jesus Garcia-Donas. A phase II study of JNJ-42756493, a pan-FGFR tyrosine kinase inhibitor, in patients with metastatic or unresectable urothelial cancer (UC) harboring FGFR gene alterations. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT080.