European Urology Open Science (Apr 2024)

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

Journal volume & issue
Vol. 62
pp. 8 – 15

Abstract

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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.

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