Phase II Pilot Trial of Tislelizumab plus Low-Dose Nab-Paclitaxel for Extensive Very High-Risk Non-Muscle-Invasive Bladder Cancer.

Abstract

Combinations of immune checkpoint inhibitors and nab-paclitaxel have improved outcomes in advanced urothelial carcinoma and muscle-invasive bladder cancer. This study evaluates the safety and efficacy of tislelizumab combined with low-dose nab-paclitaxel in extensive very high-risk non-muscle-invasive bladder cancer. TRUCE-02 was a single-arm phase II trial that included 63 patients with visually incomplete resection and/or high-volume high-grade T1 tumors (with or without carcinoma in situ) who were ineligible for or declined radical cystectomy. Patients received intravenous tislelizumab (200 mg on day 1) and nab-paclitaxel (200 mg on day 2) every 3 weeks, with assessment approximately 3 months after initial administration. The primary endpoint was the complete response (CR) rate of high-risk disease. Main secondary endpoints included safety and duration of CR. The safety analysis included all 63 patients, and the efficacy analysis included 59 patients. Thirty-seven patients (62.7%; 95% confidence interval, 49.1%-75.0%) achieved a CR of high-risk disease, with a 24-month sustained response rate of 96.3% (95% confidence interval, 89.4%-100.0%). Grade 3 to 4 treatment-related adverse events occurred in nine patients (14%), with no fatal events reported. Tislelizumab plus low-dose nab-paclitaxel was well tolerated and showed promising antitumor activity, making it a potential alternative for patients with extensive very high-risk non-muscle-invasive bladder cancer who are ineligible for or decline radical cystectomy.