Final analysis results from a multicenter clinical study of tislelizumab combined with gemcitabine and cisplatin as neoadjuvant therapy in patients with cT2-T4aN0M0 MIBC.

4585 Background: To evaluate the efficacy and safety of tislelizumab combined with gemcitabine and cisplatin as neoadjuvant therapy for patients (pts) with clinical T2-T4aN0M0 (cT2-T4aN0M0) muscle-invasive bladder urothelial cancer (MIBC). At predefined interim analysis, the study has met the first stage aim. Here reported the results of the predefined final analysis. Methods: This phase II study enrolled pts tolerated with the cisplatin therapy. Eligible pts received tislelizumab 200 mg in day 1 (D1), cisplatin 70 mg/m 2 D2, and gemcitabine 1000 mg/m 2 D1 and D8 every 21 days for four cycles. Radical cystectomy (RC) was performed within 6 weeks after last dose treatment. The primary end point was pathologic complete response (pCR, pT0N0M0). Secondary end points were pathologic downstaging (≤pT1N0M0) (pDS), EFS, OS and safety. Simon two-stage design was used. If >5 pts achieved pCR in the first stage (n=22), study would proceed to the second stage and enroll 33 additional pts. If >18 of 55 pts achieved pCR, we would deem the study to have met the primary endpoint. Results: At the data cut off time of 14 th Dec 2022, 63 pts (38 cT2, 19 cT3, and 6 cT4a) have completed neoadjuvant therapy, with median age of 64 (48-75) years. The median relative dose intensity of tislelizumab, cisplatin and gemcitabine were 92.3%, 85.7% and 85.6%, respectively. At this time, 55 pts underwent RC and completed 30 days post-surgery follow-up. The median time from last dose to RC was 4.4 (range: 0.6-13.3) weeks. Eight pts refused RC. Among 55 efficacy evaluable pts, 27 (49.1% [90% CI, 37.4-60.9]) pts achieved pCR, while 41 (74.5% [95% CI, 61.0-85.3]) pDS. Pts with cT2 achieved 55.6% (20/36) pCR and 86.1% (31/36) pDS. Among 14 non-responders, 3 of them (1 cT2, 2 cT3) achieved pT0, but with pathologic N1. Clavien-Dindo grade ≥3 postoperative complications occurred in 7.9% pts. Most common neoadjuvant therapy related AEs of any grade were hematologic toxicities (88.9%), nausea (77.8%), and vomiting (50.8%). Grade ≥3 neoadjuvant therapy related AEs occurred in 60.3% pts, which were hematologic toxicities (58.7%) in most. The frequently occurring immune-related AEs (irAEs) (>5%) included dizziness (14.3%), fatigue (12.7%), ASL/ALT increased (7.9%), rash (7.9%), pruritus (7.9%), and GGT increased (6.3%). Grade ≥3 irAEs occurred in 2 pts (pneumonia, n=1; cardiomyopathy, n=1). Conclusions: The study met its primary endpoint. Neoadjuvant tislelizumab combined with gemcitabine and cisplatin showed promising anti-tumor activity with high pCR and well tolerance in MIBC pts. Clinical trial information: ChiCTR2000037670 .