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

4580 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). Methods: This multicenter, open-label, single arm 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), 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: We reported the results in the first stage. By Oct 2021, 23 eligible pts were enrolled. Eighteen pts have completed neoadjuvant therapy, with median age of 62 (48-72) years and 8 (44.4%) pts of PD-L1 positive, among whom 17 pts underwent RC and one declined RC. At the data cut off time of 14 th Jan 2022, among 17 evaluable pts (12 cT2, 3 cT3, and 2 cT4a), 10 (58.8% [95% CI, 32.9-81.6]) pts achieved pCR and 13 (76.5% [95% CI, 50.1-93.2]) achieved pathologic downstaging. No significant differences were found in pCR (62.5% vs. 55.6%) and downstaging (75.0% vs. 77.8%) rates between pts with PD-L1 positive versus PD-L1 negative. Eighteen pts completed 71/72 cycles of tislelizumab, 68/72 cycles of cisplatin and 135/144 cycles of gemcitabine therapy. The rate of dose reduction (all due to AEs) of cisplatin and gemcitabine therapy was 25.0% (17/68 cycles) and 23.7% (32/135 cycles), respectively. The relative dose intensity of tislelizumab, cisplatin and gemcitabine were 93.6%, 84.5% and 85.9%, respectively. Most common neoadjuvant therapy related AEs of any grade were hematologic toxicities (94.4%), nausea (72.2%), vomiting (61.1%), decreased appetite (55.6%), fatigue (27.8%), pruritus (22.2%) and ALT/AST increased (22.2%). Grade ≥3 neoadjuvant therapy related AEs were neutropenia (n = 6), thrombocytopenia (n = 4), anemia (n = 2) and lymphocyte count decreased (n = 1). Eight pts experienced grade 1-2 immune related AEs, including pruritus (n = 4), rash (n = 2), ALT/AST increased (n = 4), GGT increased (n = 2), CPK increased (n = 1), hyperthyroidism (n = 1), hypothyroidism (n = 1). Conclusions: Neoadjuvant tislelizumab combined with gemcitabine and cisplatin showed promising anti-tumor activity with high pCR and well tolerance in MIBC pts. The target of first stage has been achieved, and enrollment is ongoing. At the data cut off 14 th Jan 2022, 34 pts have been enrolled. Clinical trial information: ChiCTR2000037670.