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

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

doi:10.1016/j.euros.2024.01.013

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

Eur Urol Open Sci. 2024 Feb 16:62:8-15. doi: 10.1016/j.euros.2024.01.013. eCollection 2024 Apr.

Authors

F Johannes P van Valenberg^{1

2}, Antoine G van der Heijden¹, Christopher J Cutie³, Sumeet Bhanvadia³, Kirk A Keegan^{3

4}, Shalaka Hampras⁵, Hussein Sweiti⁶, John C Maffeo³, Shu Jin³, Albert Chau⁷, Donald L Reynolds³, Crysti Iarossi³, April Kelley³, Xiang Li⁵, Katharine A Stromberg⁵, J P Michiel Sedelaar¹, Jessica J O Steenbruggen², Diederik M Somford², J Alfred Witjes¹

Affiliations

¹ Department of Urology, Radboudumc, Nijmegen, The Netherlands.
² Department of Urology, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands.
³ Janssen Research & Development, Lexington, MA, USA.
⁴ Department of Urology, Vanderbilt University, Nashville, TN, USA.
⁵ Janssen Research & Development, Raritan, NJ, USA.
⁶ Janssen Research & Development, Spring House, PA, USA.
⁷ Datacision Limited, London, UK.

Abstract

Background and objective: 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.

Methods: 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.

Key findings and limitations: 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.

Conclusions and clinical implications: 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.

Patient summary: 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.

Keywords: Gemcitabine; Intravesical drug delivery system; Intravesical therapy; Non–muscle-invasive bladder cancer; Prolonged exposure; TAR-200.