TAR-200 for Bacillus Calmette-Guérin–Unresponsive High-Risk Non–Muscle-Invasive Bladder Cancer: Results From the Phase IIb SunRISe-1 Study
Siamak Daneshmand, Michiel S. van der Heijden, Joseph Jacob, Félix Guerrero‐Ramos, Martin Bögemann, Giuseppe Simone, Christopher Michael Pieczonka, Nelson Canales Casco, Daniel Zainfeld, Philipp Spiegelhalder, Évanguelos 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, Manish Patel, Thierry Roumeguere, Charles Van Praet, Harm Arentsen, Bart De Troyer, Frederic Baekelandt, Karel Decaestecker, Girish Kulkarni, Wassim Kassouf, George Vrabec, Sabrina Falkowski, Geraldine Pignot, Evanguelos Xylinas, Morgan Roupret, Marc Colombel, Romain Mathieu, Benoit Wolff, Marc-Olivier Timsit, Xavier Artignan, Stephane Droupy, Herve Lang, Mathieu Roumiguie, Frank Bladou, Catherine Becht, Martin Bögemann, Phillipp Spiegelhalder, Jorg Klier, Tilman Toderhofer, Eva Hellmis, Petros Sountoulides, Konstantinos Hatzimouratidis, Giuseppe Simone, Luca Galli, Frederico Deho, Andrea Minervini, Andrea Necchi, Takashi Kawahara, Shuya Kandori, Masao Tsujihata, Shinji Urakami, Taek Won Kang, Ja Hyeon Ku, Kang Su Cho, Wonho Jung, Ho Kyung Seo, Jong Kil Nam, Diederik Somford, Michiel Van der Heijden, Antonio Morais, Vania Grenha, Jorge Rebola, Sandra Custodio, Vagif Atduev, Denis Kholtdobin, Jose Luis Alvarez-Ossorio Fernandez, Javier Romero Otero, Felix Guerrero Ramos, Bernardo Herrera Imbroda, Pol Servian Vives, Nelson Canales Casco, Mario Eduardo Alvarez Maestro, David Morris, Siamak Daneshmand, Curtis Dunshee, Daniel Zainfeld, Katie Murray, Laurence Belkoff, Peter Earl Clark, Yair Lotan, Joseph Jacob, David Cahn, Christopher Pieczonka, Amy Luckenbaugh, Marc Pliskin, Jason Hafron, Eugene Cone, Brian Mazzarella
Abstract
PURPOSE: 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. METHODS: 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 and 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). RESULTS: 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 to 89.8) and 25.8 months (95% CI, 8.3 to not estimable), respectively. In C4, 6-, 9-, and 12-month DFS rates were 85.3% (95% CI, 71.6 to 92.7), 81.1% (95% CI, 66.7 to 89.7), and 70.2% (95% CI, 51.6 to 82.8), respectively. In C1 and C3, CR rates were 67.9% (95% CI, 53.7 to 80.1) and 46.4% (95% CI, 27.5 to 66.1), respectively. Rates of grade ≥3 treatment-related adverse events (AEs) were 12.9%, 13.5%, 37.7%, and 7.1% in C2, C4, C1, and C3, respectively, and of serious treatment-related AEs, 5.9%, 5.8%, 15.1%, and 3.6%. No treatment-related deaths occurred. CONCLUSION: 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.