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Overview of Taris GemRIS: A Novel Drug Delivery System for Bladder Cancer – Beyond the Abstract

Intravesical chemotherapy is currently the mainstay of treatment for non-muscle invasive bladder cancer (NMIBC) but has multiple limitations leading to a ~50% recurrence rate among patients with NMIBC. Dwell time is limited by urine production and washout during voiding, which results in poor drug delivery into the urothelium and bladder wall. Intravesical implants have been proposed to overcome this barrier, including the GemRIS device by Taris Biomedical. This 5cm long semi-permeable silicone tube can be inserted and removed in the office and delivers a continuous dose of drug while implanted.1,2

Originally developed to emit lidocaine for IC patients, the device was well tolerated in phase 1 and 1b trials in interstitial cystitis patients. Building on this, the GemRIS was developed to deliver a continuous dose of gemcitabine over a period of weeks.3,4 As this should vastly improve the drug delivery of intravesical chemotherapies, the device is the subject of multiple clinical trials examining its use in a variety of clinical settings, not only in NMIBC but also in muscle invasive bladder cancer (MIBC).5,6

Thus far, the only data published from these trials comes from NCT02722538 which uses GemRIS in the neoadjuvant setting for a total of 2 weeks prior to cystectomy for MIBC patients who are cisplatin-ineligible. Of 10 subjects who received the device, 8 demonstrated a significant shrinkage in visible tumor volume at the time of cystectomy and 4 had no residual muscle invasive disease on final pathology.7,8

An additional phase 1 trial is underway investigating the safety of neoadjuvant combination GemRIS and Nivolumab in MIBC. By combining GemRIS with an immunologic checkpoint inhibitor, this study aims to demonstrate an abscopal effect whereby the systemic anti-tumor activity of Nivolumab is enhanced due to increased tumor antigen presentation from GemRIS’ local cytotoxic effect.9–12

A final MIBC trial investigates the use of long term GemRIS installations, 4 three-week treatments, in patients with MIBC who are unfit for cystectomy or chemoradiation. This palliative application would fill a treatment void in patients with limited alternatives, and could potentially reduce symptom burden and need for repeat surgeries in a comorbid population.13

Overall, the data on GemRIS is limited to a small sample of preliminary results from one of the many ongoing trials. However, these data show promise and suggest that this improved drug delivery mechanism may have a significant impact on the efficacy of intravesical chemotherapies if findings are replicated by ongoing and future studies.

Written by: Dominic Grimberg, MD, Ankeet Shah, MD, and Brant A. Inman, MD, MS, Division of Urology, Duke University Medical Center, Durham, North Carolina, USA.

References:

  1. Douglass L, Schoenberg M. The Future of Intravesical Drug Delivery for Non-Muscle Invasive Bladder Cancer. Bladder Cancer. 2(3):285-292. doi:10.3233/BLC-160056
  2. Tan WS, Kelly JD. Intravesical device-assisted therapies for non-muscle-invasive bladder cancer. Nat Rev Urol. 2018;15(11):667. doi:10.1038/s41585-018-0092-z
  3. Nickel JC, Jain P, Shore N, et al. Continuous intravesical lidocaine treatment for interstitial cystitis/bladder pain syndrome: safety and efficacy of a new drug delivery device. Sci Transl Med. 2012;4(143):143ra100. doi:10.1126/scitranslmed.3003804
  4. Safety and Tolerability Study of the Taris Placebo System - Full Text View - ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT01051336. Accessed July 22, 2019.
  5. Safety and Tolerability of TAR-200 mg in Subjects With Non-Muscle-Invasive Bladder Cancer - Full Text View - ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT02720367. Accessed July 22, 2019.
  6. Safety and Tolerability of GemRIS 225 mg in Subjects With Muscle-Invasive Bladder Cancer - Full Text View - ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT02722538. Accessed July 19, 2019.
  7. Daneshmand S, Pohar KS, Steinberg GD, Aron M, Cutie C. Effect of GemRIS (gemcitabine-releasing intravesical system, TAR-200) on antitumor activity in muscle-invasive bladder cancer (MIBC). J Clin Oncol. 2017;35(15_suppl):e16000-e16000. doi:10.1200/JCO.2017.35.15_suppl.e16000
  8. TARIS Announces Positive Results of Phase 1b Trial of TAR-200 in Muscle Invasive Bladder Cancer. Taris. June 2019. https://tarisbiomedical.com/taris-announces-positive-results-of-phase-1b-trial-of-tar-200-in-muscle-invasive-bladder-cancer/. Accessed July 19, 2019.
  9. Wersäll PJ, Blomgren H, Pisa P, Lax I, Kälkner K-M, Svedman C. Regression of non-irradiated metastases after extracranial stereotactic radiotherapy in metastatic renal cell carcinoma. Acta Oncol. 2006;45(4):493-497. doi:10.1080/02841860600604611
  10. Lui Y, Dong Y, Kong L, Shi F, Zhu H, Yu J. Abscopal effect of radiotherapy combined with immune checkpoint inhibitors | Journal of Hematology & Oncology | Full Text. https://jhoonline.biomedcentral.com/articles/10.1186/s13045-018-0647-8. Accessed July 18, 2019.
  11. Xing D, Siva S, Hanna GG. The Abscopal Effect of Stereotactic Radiotherapy and Immunotherapy: Fool’s Gold or El Dorado? Clin Oncol. 2019;31(7):432-443. doi:10.1016/j.clon.2019.04.006
  12. Safety and Tolerability of TAR-200 and Nivolumab in Subjects With Muscle-Invasive Bladder Cancer - Full Text View - ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT03518320. Accessed July 19, 2019.
  13. Safety and Tolerability of TAR-200 in Subjects With Muscle-Invasive Bladder Cancer Who Are Unfit for Radical Cystectomy - Full Text View - ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT03404791. Accessed July 19, 2019.
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