TAR-200 is a first-in-class intravesical drug-releasing system designed to provide sustained delivery of gemcitabine in the bladder. TAR-200 alone or in combination with cetrelimab (PD-1 inhibitor) could improve outcomes in patients with bacillus Calmette-Guérin (BCG)-unresponsive high-risk non-muscle-invasive bladder cancer (NMIBC) ineligible for or refusing radical cystectomy.
In this phase IIb parallel cohort study, patients with BCG-unresponsive carcinoma in situ (CIS) with/without papillary disease received TAR-200 monotherapy (Cohort 2 [C2]), TAR-200 plus cetrelimab (C1), or cetrelimab monotherapy (C3). Patients with BCG-unresponsive high-risk papillary disease-only NMIBC received TAR-200 monotherapy (C4). TAR-200 was dosed through month 24; cetrelimab through month 18. Primary end points were centrally-confirmed overall complete response (CR) rate (C1-3) or disease-free survival (DFS) rate (C4). (ClinicalTrials.gov number, NCT04640623.).
At data cutoff (March 31, 2025), 53, 85, 28, and 52 patients were treated in C1-4, respectively. In C2, CR rate and median duration of response were 82.4% (95% CI, 72.6-89.8) and 25.8 months (95% CI, 8.3-not estimable), respectively. In C4, 6-, 9-, and 12-month DFS rates were 85.3% (95% CI, 71.6-92.7), 81.1% (95% CI, 66.7-89.7), and 70.2% (95% CI, 51.6-82.8), respectively. In C1 and C3, CR rates were 67.9% (95% CI, 53.7-80.1) and 46.4% (95% CI, 27.5-66.1), respectively. Rates of grade ≥3 treatment-related adverse events were 12.9%, 13.5%, 37.7%, and 7.1% in C2, C4, C1, and C3, respectively, and of serious treatment-related adverse events, 5.9%, 5.8%, 15.1%, and 3.6%. No treatment-related deaths occurred.
TAR-200 monotherapy was well tolerated, with a high CR rate, durable responses, and prolonged DFS in patients with BCG-unresponsive high-risk NMIBC. TAR-200 monotherapy offered a more favorable risk-benefit profile versus TAR-200 plus cetrelimab or cetrelimab alone in BCG-unresponsive CIS.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2025 Jul 30 [Epub ahead of print]
Siamak Daneshmand, Michiel S Van der Heijden, Joseph M Jacob, Felix Guerrero-Ramos, Martin Bögemann, Giuseppe Simone, Christopher M Pieczonka, Nelson Canales Casco, Daniel Zainfeld, Philipp Spiegelhalder, Evanguelos Xylinas, David Cahn, Yair Lotan, Katie S Murray, Takashi Kawahara, Katharine Stromberg, Jason Martin, Abhijit Shukla, Christopher J Cutie, Kristi Bertzos, Shalaka Hampras, Hussein Sweiti, Andrea Necchi
University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA., Netherlands Cancer Institute, Amsterdam, Netherlands., Upstate Medical University, Syracuse, NY., Hospital Universitario 12 de Octubre, Madrid, Spain., Münster University Hospital, Münster, Germany; West German Cancer Center, Münster, Germany., 'Regina Elena' National Cancer Institute, Rome, Italy., Associated Medical Professionals of New York (an affiliate of US Urology Partners), Syracuse, NY., Hospital de Jerez de la Frontera y Punta Europa, Cádiz, Spain., Urology San Antonio, San Antonio, TX., Urologie Neandertal, Gemeinschaftspraxis für Urologie, Mettmann, Germany., Bichat-Claude Bernard Hospital, Assistance Publique-Hôpitaux de Paris, Université de Paris Cité, Paris, France., Colorado Urology, Lakewood, CO., UT Southwestern Medical Center, Dallas, TX., NYU Langone Health, New York, NY., Yokohama City University Medical Center, Yokohama, Japan., Johnson & Johnson, Raritan, NJ., Johnson & Johnson, High Wycombe, UK., Johnson & Johnson, Lexington, MA., Johnson & Johnson, Horsham, PA., Johnson & Johnson, Spring House, PA., IRCCS San Raffaele Hospital, Milan, Italy.
PubMed http://www.ncbi.nlm.nih.gov/pubmed/40737582