TRUCE-11: An open-label, single-arm, multicenter phase II study of tislelizumab combined with nab-paclitaxel for muscle-invasive urothelial bladder carcinoma.

4618 Background: Neoadjuvant tislelizumab plus nab-paclitaxel may enhance pathologic response in muscle-invasive bladder cancer (MIBC), and TRUCE-11 evaluates its efficacy and safety prior to radical cystectomy (RC). Methods: TRUCE-11 is a multicenter phase II neoadjuvant study for eligible MIBC pts who had pure or mixed urothelial carcinoma of the bladder (cT2–4aNxM0). Pts received nab-paclitaxel 125 mg/m² IV on day 1, followed 2 h later by tislelizumab 200 mg IV (Q3W) for 2–3 cycles, then underwent RC with pathologic assessment. Imaging and urine cytology were performed at baseline and post-treatment. The primary endpoint was pathologic complete response (pCR). Secondary endpoints included pathologic downstaging rate (PaIR, ≤pT1), adverse events (AEs), and overall survival (OS). Exploratory analyses evaluated radiomics features (bladder MRI, PET/CT, and contrast-enhanced ultrasound) and serum biomarkers, including peripheral blood tumor whole-genome chromosomal aberration assay (PB-TWGCA). Transcriptomic biomarker discovery further highlighted GRHL1 using bulk RNA-seq and paired baseline/RC tumor scRNA-seq. Results: Between March 2024 and January 2026, 27 pts were enrolled; 21 underwent RC after neoadjuvant therapy. Among RC pts (n=21), 11 pts achieved pCR (52%) and 13 achieved PaIR (≤pT1, 62%). The most common grade 1–2 AEs were alopecia (86%), fatigue (76%), rash (43%), decreased appetite (38%), and fever (14%). No grade 3–4 AEs (CTCAE) were observed. After a median follow-up of 247 days (range, 65–677), all pts were alive. Among pts achieving pCR, pre-cystectomy MRI (DWI/ADC) showed no residual diffusion restriction and/or PET/CT showed no malignant findings, concordant with pathology. In 6 pCR pts with contrast-enhanced ultrasound, 5 (83%) demonstrated marked reduction or disappearance of tumor hypervascularity during treatment. In 5 pts, PB-TWGCA r-score was consistent with tumor burden. Transcriptomic analyses further suggested that tumor-cell GRHL1 expression might be underlying markers that predict adverse outcomes for the pCR and non-pCR pts cohorts in this crew. Conclusions: Neoadjuvant tislelizumab plus nab-paclitaxel achieved a high pCR and downstaging rate with no grade 3–4 AEs in pts with MIBC undergoing RC. Multimodal imaging and circulating/transcriptomic biomarkers (PB-TWGCA r-score and tumor-cell GRHL1) may aid response evaluation and require confirmation in larger cohorts. Clinical trial information: NCT05328336 .