LBA104 - First safety and efficacy results of the TAR-210 erdafitinib (erda) intravesical delivery system in patients (pts) with non–muscle-invasive bladder cancer (NMIBC) with select FGFR alterations (alt)

Background

Treatment (tx) options are limited in NMIBC that recurs after intravesical chemotherapy or bacillus Calmette-Guérin (BCG). TAR-210 is a novel intravesical drug delivery system designed to provide local, continuous release of erda (selective pan-FGFR tyrosine kinase inhibitor) within the bladder while limiting systemic toxicities. This open-label, multicenter phase 1 study (NCT05316155) evaluates the safety, PK, and efficacy of TAR-210 in pts with NMIBC whose tumors harbor select FGFRalt.

Methods

FGFRalt were identified in tumor tissue or urine cell-free DNA. Cohort 1 (C1) pts had recurrent, BCG-experienced high-risk NMIBC (high-grade Ta/T1; papillary only) and refused or were ineligible for radical cystectomy. Cohort 3 (C3) pts had recurrent, intermediate-risk NMIBC (Ta/T1) with history of only low-grade papillary disease. Before tx, C1 pts must have all visible disease resected; C3 requires the presence of visible tumors. TAR-210 systems with 2 different erda release rates were evaluated. Response is assessed every 3 mo with continued tx for up to 1 year if recurrence-free (RF) (C1) or in complete response (CR) (C3).

Results

As of Aug 29, 2023, 16 pts in C1 and 27 pts in C3 have been treated; 11 and 15 pts, respectively, had ≥1 response assessment. 82% in C1 were RF; 87% in C3 achieved CR (Table). Most common tx-related AEs were grade 1/2 lower urinary tract AEs. There were no dose-limiting toxicities, no deaths, 2 pts discontinued due to AEs of low-grade urinary symptoms, and 1 pt had serious AEs of pyelonephritis and sepsis. PK showed sustained erda concentrations in urine, with very low plasma exposures. Table: LBA104

Efficacy outcomes and Tx exposure

CI, confidence interval; mo, months; NE, non-estimable; RF, recurrence-free; RFS, recurrence-free survival. *All CR in Cohort 3 were ongoing as of data cutoff.

Conclusions

TAR-210 appears safe and well tolerated with predominantly low-grade urinary system AEs and high CR rate and RF survival in pts with NMIBC with FGFRalt. Results justify further study of targeted tx of erda using a novel intravesical delivery system in early-stage bladder cancer.

Clinical trial identification

NCT04083976.

Editorial acknowledgement

Medical writing assistance was provided by Ira Mills, PhD, of Parexel and was funded by Janssen Global Services, LLC.

Legal entity responsible for the study

Janssen Research & Development.

Funding

Janssen Research & Development.

Disclosure

G. Jayram: Financial Interests, Personal, Advisory Board: Merck, AstraZeneca; Financial Interests, Personal, Invited Speaker: Photocure, BMS; Financial Interests, Institutional, Steering Committee Member: Janssen; Financial Interests, Institutional, Local PI: Merck. N.D. Shore: Financial Interests, Personal, Advisory Board: AbbVie, Amgen, Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Boston Scientific, Clovis Oncology, Cold Genesys, Dendreon, Exact Imaging, Exact Sciences, FerGene, Genesis Care Us, Invitae, Janssen, MDxhealth, Merck, Myovant, Myriad, Nymox, Pacific Edge, Pfizer, Propella, PreView, Sanofi Genzyme, Speciality Networks, Sesen Bio, Tolmar, Urogen, Clarity, Lantheus, Lilly, Photocure, Telix, Photocure, Vaxiion, Foundation Medicine, Asieris, Alessa Therapeutics, Akido, Arquer, Fize Medical, GConcology, Genetech, Guardant, Ferring, Immunitybio, Incyte, Minomic, NGM, Nonagen, Novartis, PlatformQ, Profound, Promaxo, Protara, Vessi; Financial Interests, Personal, Member of Board of Directors: Photocure. D. Zainfeld: Financial Interests, Personal, Advisory Board: AstraZeneca, Immunity Bio, Bristol Myers Squibb. J. Meeks: Financial Interests, Personal, Speaker, Consultant, Advisor: Janssen. F. Roghmann: Financial Interests, Personal, Advisory Board: Janssen, Roche, Merck, Pfizer, QED; Financial Interests, Personal, Invited Speaker: MSD, AstraZeneca. S. Daneshmand: Financial Interests, Personal, Speaker, Consultant, Advisor: Photocure, Taris, Ferring, and QED Therapeutics; Financial Interests, Personal, Other, Honoraria: Photocure, QED Therapeutics, Olympus, Ferring, Pacific Edge, Johnson & Johnson, Aduro Biotech, Janssen, Bristol Myers Squibb, and Allergan; Financial Interests, Personal, Other, research funding and reimbursement for travel, accommodations, or expenses: Photocure; Financial Interests, Personal, Stocks or ownership: Taris. N. Beeharry: Financial Interests, Personal, Other, Employment: Janssen; Financial Interests, Personal, Stocks or ownership: Johnson & Johnson. C. Cost: Financial Interests, Personal, Other, Employment: Janssen ; Financial Interests, Personal, Stocks or ownership: Johnson & Johnson. A. Kalota: Financial Interests, Personal, Other, Employment: Janssen; Financial Interests, Personal, Stocks or ownership: Johnson & Johnson. J. Lauring: Financial Interests, Personal, Stocks or ownership: Johnson & Johnson; Financial Interests, Personal, Other, Employment: Janssen. M. Peterson: Financial Interests, Personal, Other, Employment: Janssen; Financial Interests, Personal, Stocks or ownership: Johnson & Johnson. M. Quiroz: Financial Interests, Personal, Other, Employment: Janssen; Financial Interests, Personal, Stocks or ownership: Johnson & Johnson. N. Stone: Financial Interests, Personal, Other, Employment: Janssen; Financial Interests, Personal, Stocks or ownership: Johnson & Johnson. W. Zhu: Financial Interests, Personal, Other, Employment: Janssen; Financial Interests, Personal, Stocks or ownership: Johnson & Johnson. F. Guerrero-Ramos: Financial Interests, Personal, Speaker, Consultant, Advisor: Janssen, Pfizer, Roche, Combat Medical; Financial Interests, Personal, Other, honoraria: Combat Medical, Janssen, Pfizer; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Combat Medical, Janssen, Pfizer; Financial Interests, Personal, Advisory Board: Janssen, AstraZeneca. All other authors have declared no conflicts of interest.