A phase II clinical trial of intravesical YH01 for BCG-unresponsive high-risk non–muscle-invasive bladder cancer (NMIBC).

Abstract

e16612 Background: Non–muscle-invasive bladder cancer (NMIBC) accounts for approximately 70–80% of bladder cancer cases. Nearly 45% of high-risk patients experience recurrence or progression within one year after Bacillus Calmette-Guérin (BCG) therapy and develop BCG-unresponsive disease. YH01 is a recombinant oncolytic adenovirus with modified capsid proteins to enhance tumor targeting and oncolytic activity in BCG-unresponsive disease. Methods: This open-label, multicenter Phase II trial was conducted in two stages (Phase IIa and IIb). All subjects received intravesical instillation of 75 mL YH01 injection (1×10¹⁰ IFU/mL) per dose. Phase IIa included three treatment groups: ① Treatment Group 1: Induction instillation 1-3 times (once weekly for the first 1-3 weeks), and maintenance instillation (once during the first week of each cycle); ② Treatment Group 2: Induction instillation 4-6 times (once weekly for the first 4-6 weeks), maintenance instillation protocol identical to Group 1; ③ Treatment Group 3: Induction instillation 6 times (once weekly for the first 6 weeks), consolidation instillation 3 times (once every 2 weeks for the first 6 weeks), maintenance instillation 3 times (once every 4 weeks), followed by once every 12 weeks. Patients in Groups 2 and 3 with recurrence could receive a second course of induction instillation. Results: A total of 13 patients were enrolled at this center in Phase IIa (with a median follow-up of 9.4 months), distributed across all three treatment groups. Efficacy outcomes: Group 1 (n = 3), 1 patient recurred, 1 progressed, and 1 achieved Complete Response (CR). In Group 2 (n = 3), 1 patient recurred and 2 achieved CR. In Group 3 (n = 7), all patients (100%) achieved CR. The overall response rate (ORR) was 76.9%. Safety results: A total of 61 adverse events (AEs) were reported, of which 67.2% were Grade 1 and 32.8% were Grade 2. Grade 2 AEs occurred in 8 patients (61.54%). The most common Grade 1 AEs included increased urinary white blood cell count, hematuria, anemia, and decreased lymphocyte count. The most frequent Grade 2 AE was urinary tract infection (9 events), followed by hyperbilirubinemia and increased urinary white blood cell count. No Grade 3 or higher AEs were observed, and the overall safety profile was favorable and manageable. Conclusions: Following dose-exploration, Group 3 achieved a 100% complete response (CR) rate. These findings suggest that intravesical YH01 injection demonstrates promising preliminary efficacy and a favorable safety profile for BCG-unresponsive or failed intermediate/high-risk NMIBC. YH01 represents a viable novel alternative for patients who are ineligible for or refuse radical cystectomy.