The Safety, Tolerability, and Preliminary Efficacy of a Gemcitabine-releasing Intravesical System (TAR-200) in American Urological Association-defined Intermediate-risk Non-muscle-invasive Bladder Cancer Patients: A Phase 1b Study.

Patients with intermediate-risk non-muscle-invasive bladder cancer (IR NMIBC) have a high risk of recurrence and need effective therapies to reduce the risk of disease recurrence or progression. This phase 1b study (NCT02720367) assessed the safety and tolerability of TAR-200, an intravesical drug delivery system, in participants with IR NMIBC.

Participants with recurrent IR NMIBC were eligible. Participants received either two 7-d or two 21-d TAR-200 dosing cycles over a 4-6-wk period in a marker lesion/ablation design. TAR-200 was placed in the window between the cystoscopy showing recurrent papillary disease and the subsequent complete transurethral resection of the bladder tumour. The primary endpoint was TAR-200 safety. The secondary endpoints included TAR-200 tolerability, pharmacokinetics, and preliminary efficacy.

Twelve participants received TAR-200 treatment. No TAR-200-related serious or grade ≥ 3 treatment-emergent adverse events (TEAEs) occurred. Nine participants had grade ≤ 2 TAR-200-related TEAEs, with urgency, dysuria, and haematuria being most common. Two participants refused a second dosing cycle due to urinary urgency and frequency. Insertion and removal of TAR-200 was successful in all cases. Plasma gemcitabine concentrations remained below the lower limit of detection. Five participants (42%) had complete response (CR): four had pathological CR and one had CR based on visual assessment.

TAR-200 appears to be safe and well tolerated, with encouraging preliminary efficacy in participants with IR NMIBC. This study lays the groundwork for the multiple phase 2 and 3 global studies that are currently on-going for TAR-200.

In this study, researchers evaluated the safety of the novel drug delivery system TAR-200 in participants with intermediate-risk non-muscle-invasive bladder cancer. They concluded that TAR-200 was safe and well tolerated with promising antitumour activity.

European urology open science. 2024 Feb 16*** epublish ***

F Johannes P van Valenberg, Antoine G van der Heijden, Christopher J Cutie, Sumeet Bhanvadia, Kirk A Keegan, Shalaka Hampras, Hussein Sweiti, John C Maffeo, Shu Jin, Albert Chau, Donald L Reynolds, Crysti Iarossi, April Kelley, Xiang Li, Katharine A Stromberg, J P Michiel Sedelaar, Jessica J O Steenbruggen, Diederik M Somford, J Alfred Witjes

Department of Urology, Radboudumc, Nijmegen, The Netherlands., Janssen Research & Development, Lexington, MA, USA., Janssen Research & Development, Raritan, NJ, USA., Janssen Research & Development, Spring House, PA, USA., Datacision Limited, London, UK., Department of Urology, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands.