PUNCH01: Interim results from a phase II study of intra-arterial chemotherapy (IAC) combined with tislelizumab and bacillus Calmette-Guerin (BCG) in high-risk non-muscle-invasive bladder cancer (HR NMIBC).

767 Background: Our study was established to evaluate the efficacy and safety of IAC combined with tislelizumab and BCG as a bladder-preserving treatment for HR NMIBC pts. Methods: This open-label, single arm phase II study enrolled BCG-naïve HR NMIBC pts with papillary tumors (high-grade Ta or T1 tumors). Firstly, the papillary tumors should be removed all visible lesions by TURBT. Secondly, angiographic catheter was placed into the internal iliac arteries with Seldinger’s percutaneous technique, cisplatin (60 mg/m 2 ) and epirubicin (50 mg/m 2 ) were administered arterially in day 1 (D1), every 3 weeks for 2-4 cycles. And pts received tislelizumab 200 mg ivgtt in D1, every 3 weeks for 2-4 cycles. Finally, pts received 18 instillations of BCG plus at least 8 cycles of tislelizumab (200 mg ivgtt, every 3 weeks). Specifically, pts were started on an induction course of BCG with 6 instillations every week, followed by maintenance with 3 instillations every 2 weeks and 9 instillations every 4 weeks. The primary end point was disease-free survival(DFS) rate at 12 months. Secondary end points were bladder-preservation rate, OS and safety. Our study estimated a DFS rate at 12 months was no less than 55% and the study would enroll 29 pts. Results: By Jul. 2024, 23 eligible pts were enrolled. Twenty-two pts were analyzed (male 90.9%; median age 61 years(37-80); pure TCC 80.0%; median tumor size 3.0 cm (0.4-8.0); multiple papillary tumours=72.7%; high-gradeTa=54.5%, T1=45.5%). Median follow-up was 11.4 months (6.0-40.3), the mean number of IAC cycles was 2.7, mean number of tislelizumab cycles was 8.3, and the median BCG instillations was 10 (6-18). The DFS rate at 12month was 100.0% (95%CI, 63.8%-100%). The bladder-preservation rate at 12 months was 100% (95%CI,100%-100%). The OS rate at 12 months was 100% (95%CI, 100%-100%). 18 pts experienced treatment related adverse events, including nausea (n=6, G2), neutropenia (n=4, G2), fatigue (n=3, G2), increased AST/ALT (n=3,G2), fever (n=2, G3) and myalgia (n=1, G2). Conclusions: Our interim results supported the use of IAC combined with tislelizumab and BCG as a promising bladder-preserving strategy for HR NMIBC pts. Clinical trial information: ChiCTR2200067156 .