Tislelizumab combined with gemcitabine as first-line treatment in cisplatin-ineligible patients with locally advanced or metastatic urothelial carcinoma: a single center, single-arm phase 2 trial.

Patients with la/mUC have an unfavorable prognosis and limited treatment options, particularly those who were considered ineligible for cisplatin-containing therapeutic schedule. ICIs have played a significant therapeutic role among this group of patients. Ongoing clinical investigations continue to explore the utility of ICIs, both used alone or in combination with other treatment methods. The purpose of this clinical trial is to explore the efficacy and safety of gemcitabine combined with tislelizumab as initial treatment for the la/mUC patients who are intolerant to platinum-based drugs. Primary endpoints were ORR and DCR. Secondary endpoints comprised PFS and OS. At the data cutoff (September 1, 2025), 30 patients were enrolled. As the results display, the mPFS was 13.9 months (95% CI: 11.4-16.3), and the mOS was 23.3 months ([IQR]: 14.4-33.1; 95% CI: 18.2-28.3).The confirmed ORR was 46.7% (14/30; 95% CI: 28.3-65.7), DCR was 76.7%. The most frequent TRAEs were hematological toxicities, including leukopenia (43.3%) and neutropenia (40.0%). We also explored the predictive potential of tumor-associated TLS as an innovative analysis. There was a quantitative difference in ORR according to the results of TLS analysis, with response rates of 66.7% (n=9) in TLS positive group and 35.3% (n=17) in negative group. However, this observed change did not reach statistical significance (P = 0.218). In conclusion, the combination of tislelizumab and gemcitabine demonstrated manageable tolerability and a promising preliminary efficacy signal as first-line therapeutic strategy for la/mUC patients who cannot receive cisplatin-containing regimen and warrants further investigation. https://www.chictr.org.cn/index.html, identifier ChiCTR2200061631.