LBA01-10 INTERIM RESULTS FROM A PHASE 1B CLINICAL TRIAL EVALUATING TOLERABILITY AND ACTIVITY OF FGFR INHIBITION IN LOCALIZED UPPER TRACT UROTHELIAL CARCINOMA (UTUC)

Abstract

You have accessJournal of UrologyCME1 May 2022LBA01-10 INTERIM RESULTS FROM A PHASE 1B CLINICAL TRIAL EVALUATING TOLERABILITY AND ACTIVITY OF FGFR INHIBITION IN LOCALIZED UPPER TRACT UROTHELIAL CARCINOMA (UTUC) Surena Matin, Mehrad Adibi, Amishi Shah, Omar Alhalabi, Paul Corn, Charles Guo, Rhenita Amirtharaj, Marisa Lozano, Lianchun Xiao, Sumanta Pal, and Matthew Campbell Surena MatinSurena Matin More articles by this author , Mehrad AdibiMehrad Adibi More articles by this author , Amishi ShahAmishi Shah More articles by this author , Omar AlhalabiOmar Alhalabi More articles by this author , Paul CornPaul Corn More articles by this author , Charles GuoCharles Guo More articles by this author , Rhenita AmirtharajRhenita Amirtharaj More articles by this author , Marisa LozanoMarisa Lozano More articles by this author , Lianchun XiaoLianchun Xiao More articles by this author , Sumanta PalSumanta Pal More articles by this author , and Matthew CampbellMatthew Campbell More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002669.10AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Infigratinib is a potent oral inhibitor of FGFR1-3 with activity in metastatic urothelial cancer (response rate [RR], 25.4%), particularly in patients with metastatic UTUC (RR 50%) (Dizman et al ASCO 2020). We initiated a biomarker-informed preoperative study of infigratinib in patients with localized UTUC. METHODS: Patients with low-grade, or localized cis-platin ineligible high-grade UTUC, undergoing either ureteroscopic (URS) management or nephroureterectomy/ureterectomy (NU/U), were enrolled on a preoperative phase 1b trial (NCT04228042). Enrollment required a GFR of 30 or greater, sufficient biopsy tissue for mutational analysis, and a tumor map of all residual tumors after endoscopic biopsy and any ablation. Treatment consisted of once-daily infigratinib 125 mg (21 days of 28-day cycle) for 2 cycles. A second tumor map based on URS or NU/U was completed after cycle 2. Tolerability was assessed by ongoing monitoring and predefined stopping boundaries. The primary endpoint was tolerability, and the secondary endpoint was objective response based on tumor mapping, with a total planned enrollment of 20 patients. Targeted sequencing was performed using a NovaSeq 6000 solid tumor panel covering 610 somatic alterations including 33 fusions. RESULTS: From May 2021 until Feb 2022, 12 patients were enrolled (Table). Of 11 evaluable patients, 9 completed therapy and 2 continue on treatment. Of the 9 patients completing therapy, 2 had toxicities preventing the full duration of treatment. 4 of 9 (44%) patients had a response with tumor reduction (range 25-83%); all responders had FGFR3 mutations. Most non-responders had a prior history of bladder cancer and 1 had FGFR3-TACC3 fusion. CONCLUSIONS: Infigratinib shows substantial activity in patients with localized UTUC bearing FGFR3 mutations, consistent with previous data in the metastatic setting. Enrollment continues, and based on these promising initial results, a phase 2 expansion evaluating additional cycles is planned. Source of Funding: The trial was sponsored by QED Therapeutics. Sponsor had no involvement with data acquisition, analysis, or drafting of abstract © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e1039 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Surena Matin More articles by this author Mehrad Adibi More articles by this author Amishi Shah More articles by this author Omar Alhalabi More articles by this author Paul Corn More articles by this author Charles Guo More articles by this author Rhenita Amirtharaj More articles by this author Marisa Lozano More articles by this author Lianchun Xiao More articles by this author Sumanta Pal More articles by this author Matthew Campbell More articles by this author Expand All Advertisement PDF DownloadLoading ...