TAR-200 for Bacillus Calmette-Guérin-Unresponsive High-Risk Non-Muscle-Invasive Bladder Cancer: Results From the Phase IIb SunRISe-1 Study.

作者信息

Daneshmand Siamak, Van der Heijden Michiel S, Jacob Joseph M, Guerrero-Ramos Felix, Bögemann Martin, Simone Giuseppe, Pieczonka Christopher M, Casco Nelson Canales, Zainfeld Daniel, Spiegelhalder Philipp, Xylinas Evanguelos, Cahn David, Lotan Yair, Murray Katie S, Kawahara Takashi, Stromberg Katharine, Martin Jason, Shukla Abhijit, Cutie Christopher J, Bertzos Kristi, Hampras Shalaka, Sweiti Hussein, Necchi Andrea

机构信息

University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA.

Netherlands Cancer Institute, Amsterdam, the Netherlands.

出版信息

J Clin Oncol. 2025 Jul 30:JCO2501651. doi: 10.1200/JCO-25-01651.

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.