Urine-based molecular testing identifies FGFR alteration-positive patients for treatment with TAR-210

BackgroundSelect alterations in fibroblast growth factor receptor (FGFR) genes may be oncogenic drivers in bladder cancer. TAR-210 is a novel targeted releasing system that provides local, sustained delivery of erdafitinib, a pan-FGFR inhibitor, within the bladder. TAR-210 is being evaluated in a first-in-human clinical study (NCT05316155) in patients (pts) with early-stage bladder cancer whose tumors harbor select FGFR alterations (alt). The ability to effectively identify tumors with select FGFRalts is paramount but is hampered by limited tumor material for tissue-based tests. To overcome this challenge, a urine-based assay was implemented into the molecular screening strategy. We report early results of FGFRalt detection via the urine assay for pt selection.MethodsBladder tumor samples were tested via Qiagen therascreen® FGFR RT-PCR assay and urine samples via PredicineCARE™ next-generation sequencing assay. Select FGFRalts detected by either test was sufficient for molecular eligibility.ResultsThe FGFRalt prevalence and type detected in tissue and urine samples from screened pts with high-risk non-muscle invasive bladder cancer (HR NMIBC) or intermediate-risk (IR) NMIBC are shown in the table. Table: 1973P HR NMIBC IR NMIBC Number of samples that yielded an FGFRalt result Tissue (n=95) Urine (n=96) Tissue (n=103) Urine (n=89) FGFRalt+ rate (within samples that yielded a result), % 36.5 32.3 71.8 55.1 FGFRalts detected, % (n=23) (n=22) (n=80) (n=52) FGFR3 R248C 8.7 0 12.5 11.5 FGFR3 S249C 73.9 63.6 46.3 53.8 FGFR3 G370C 0 0 5.0 0 FGFR3 Y373C 8.7 27.3 35.0 25.0 FGFR3-TACC3v1 (fusion) 8.7 4.5 1.3 3.8 The FGFRalt+ rates and frequency of type of alt identified by urine is comparable with tissue. As of March 2024, of 21 HR-NMIBC or 31 disease-evaluable IR-NMIBC (who had visible lesions at treatment initiation) pts, 6/21 (28.6%) and 9/31 (29.0%), respectively, were enrolled based on a “urine-only� FGFRalt result. Of the pts enrolled by urine-only, all 6 HR-NMIBC pts were recurrence free and all 9 IR-NMIBC pts had a complete response at the first disease evaluation at 3 months.ConclusionsUrine testing identifies additional NMIBC pts who may respond to erdafitinib, which is especially valuable when the parallel tissue sample submitted does not return a result. Findings support urine testing for pt selection in the recently initiated phase 3 study (MoonRISe-1, NCT06319820).Clinical trial identificationNCT05316155.Editorial acknowledgementWriting assistance was provided by Ira Mills, PhD, of Parexel.Legal entity responsible for the studyJanssen Research & Development, LLC, a Johnson & Johnson Company.FundingJanssen Research & Development, LLC, a Johnson & Johnson Company.DisclosureF. Guerrero-Ramos: Financial Interests, Personal, Speaker, Consultant, Advisor: Janssen, Pfizer, Roche, Combat Medical; Financial Interests, Personal, Other, honoraria/Travel support: Combat Medical, Janssen, Pfizer ; Financial Interests, Personal, Advisory Board: Janssen, Pfizer, AstraZeneca, Bristol Myers Squibb. A. Vilaseca: Financial Interests, Personal, Speaker, Consultant, Advisor: Accord, Astellas, and Janssen; Financial Interests, Personal, Other, Travel Support: Astellas, Janssen, and Recordati. N.D. Shore: Financial Interests, Personal, Advisory Board: AbbVie, Amgen, Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Boston Scientific, Cold Genesys, Dendreon, Exact Imaging, Genesis Care Us, Invitae, Janssen, MDxhealth, Merck, Myovant, Myriad, Nymox, Pacific Edge, Pfizer, Propella, Sanofi Genzyme, Speciality Networks, Tolmar, Urogen, Clarity, Lantheus, Lilly, Photocure, Telix, Photocure, Asieris, Alessa Therapeutics, Arquer, Fize medical, GConcology, Guardant, Ferring, Foundation Medicine, Immunitybio, Incyte, Minomic, NGM, Nonagen, Novartis, PlatformQ, Promaxo, Protara, Accord, Antev, Aura biosciences, Sumitomo; Financial Interests, Personal, Member of Board of Directors: Photocure, Alessa Theraputics; Financial Interests, Personal and Institutional, Local PI: AstraZeneca, Bayer, Aura, Exact Imaging, Janssen, Merck, Myovant, Novartis, Pfizer, Propella, Bristol Myers Squibb, Dendreon, Pfizer, Urogen; Financial Interests, Institutional, Local PI: Alessa, GC oncology, Forma Therapeutics, Pacific Edge, Point Biopharma, The MT group, Theralase, Verity, Astellas, Palette Life Sciences, Steba, Zenflow. J. Meeks: Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, Incyte, Bristol Myers Squibb, Imvax, Janssen, Merck, Pfizer, Prokarium, Seagen/Astellas, and UroGen. R. Li: Financial Interests, Personal, Other, Trial Protocol Committee: CG Oncology; Financial Interests, Personal, Speaker, Consultant, Advisor: BMS, Ferring, Fergene, Arquer Diagnostics. S. Daneshmand: Financial Interests, Personal, Research Grant: Photocure; Financial Interests, Personal, Speaker, Consultant, Advisor: Ferring, Photocure, QED Therapeutics, and Taris; Financial Interests, Personal, Other, Honoraria: Aduro Biotech, Allergan (immediate family member), Bristol Myers Squibb, Ferring, Janssen, Johnson & Johnson, Olympus, Photocure, Pacific Edge, and QED Therapeutics; Financial Interests, Personal, Stocks or ownership: Taris. G. Jayram: Financial Interests, Personal, Research Grant: AstraZeneca, Blue Earth, Bristol Myers Squibb, Janssen, and Merck; Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, Blue Earth, Bristol Myers Squibb, Janssen, Merck, and Photocure; Financial Interests, Personal, Other, Honoraria: AstraZeneca, Blue Earth, Bristol Myers Squibb, Janssen, KDx Diagnostics, Merck, and Photocure; Financial Interests, Personal, Other, Travel reimbursement: AstraZeneca, Blue Earth, Bristol Myers Squibb, Janssen, Merck, Photocure, and SN; Financial Interests, Personal, Stocks or ownership: KDx Diagnostics. N. Beeharry, J. Zhang, D. Weingeist, D.A. Smirnov, C. Cost, A. Kalota, J. Lauring, N. Stone, S. Thomas: Financial Interests, Personal, Other, Employment: Janssen; Financial Interests, Personal, Stocks/Shares: Janssen. B. Brunton: Financial Interests, Personal, Advisory Board, Employment: Janssen; Financial Interests, Personal, Stocks/Shares: Janssen. All other authors have declared no conflicts of interest.