Treatment options for recurrent high-risk non-muscle-invasive bladder cancer (HR NMIBC) and muscle-invasive bladder cancer (MIBC) are limited, highlighting a need for clinically effective, accessible, and better-tolerated alternatives. In this review we examine the clinical development program of TAR-200, a novel targeted releasing system designed to provide sustained intravesical delivery of gemcitabine to address the needs of patients with NMIBC and of those with MIBC. We describe the concept and design of TAR-200 and the clinical development of this gemcitabine intravesical system in the SunRISe portfolio of studies. This includes 3 phase I studies evaluating the safety and initial tumor activity of TAR-200 and 5 phase II/III studies assessing the efficacy and safety of TAR-200, with or without systemic cetrelimab, as a treatment option for patients with HR NMIBC (bacillus Calmette-Guérin naive [papillary and carcinoma in situ] and MIBC (neoadjuvant and patients ineligible for or refusing radical cystectomy). Pharmacokinetics demonstrate intravesical gemcitabine delivery via TAR-200 over a prolonged period without detectable plasma levels. Phase I studies showed that TAR-200 is well tolerated, with preliminary antitumor activity in intermediate-risk NMIBC and MIBC. Preliminary data from the phase IIb SunRISe-1 study demonstrate that TAR-200 monotherapy is safe and effective in patients with bacillus Calmette-Guérin-unresponsive high-risk NMIBC. TAR-200 represents an innovative approach to the local treatment of bladder cancer.
Urologic oncology. 2025 Jan 15 [Epub ahead of print]
Siamak Daneshmand, Ashish M Kamat, Neal D Shore, Joshua J Meeks, Matthew D Galsky, Joseph M Jacob, Michiel S van der Heijden, Stephen B Williams, Thomas Powles, Sam S Chang, James W F Catto, Sarah P Psutka, Félix Guerrero-Ramos, Evanguelos Xylinas, Makito Miyake, Giuseppe Simone, Karen Daniel, Hussein Sweiti, Christopher Cutie, Andrea Necchi
Department of Urology, University of Southern California, Norris Comprehensive Cancer Center, Los Angeles, CA. Electronic address: ., Department of Urology, University of Texas MD Anderson Cancer Center, Houston, TX., Carolina Urologic Research Center, Myrtle Beach, SC., Department of Urology, Northwestern University, Feinberg School of Medicine, Chicago, IL., Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY., Department of Urology, Upstate Medical University, Syracuse, NY., Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, Netherlands., Division of Urology, University of Texas Medical Branch, Galveston, TX., Department of Genitourinary Oncology, Barts Cancer Institute, Queen Mary University of London, London, UK., Department of Urology, Vanderbilt University Medical Center, Nashville, TN., Division of Clinical Medicine, School of Medicine & Population Health, University of Sheffield, Sheffield, UK., Department of Urology, University of Washington, Fred Hutchinson Cancer Center, Seattle, WA., Oncologic Urology Unit, Department of Urology, Hospital Universitario 12 de Octubre, Madrid, Spain., Department of Urology, Bichat-Claude Bernard Hospital, Assistance Publique-Hôpitaux de Paris, Université de Paris Cité, Paris, France., Department of Urology, Nara Medical University, Kashihara, Nara, Japan., Department of Urology, IRCCS "Regina Elena" National Cancer Institute, Rome, Italy., Janssen Research & Development, Lexington, MA., Janssen Research & Development, Spring House, PA., Vita-Salute San Raffaele University and IRCCS San Raffaele Hospital, Milan, Italy; Department of Medical Oncology, IRCCS San Raffaele University, Milan, Italy.