Progress of phase II study of MVR-T3011, an IL-12/anti-PD-1 armed oncolytic HSV-1, in high-risk BCG-unresponsive CIS and papillary NMIBC.

4608 Background: MVR-T3011 is a novel Phase II oncolytic immunotherapy candidate based on herpes simplex virus type 1 (HSV-1). It combines potent tumor lysis with co-expression of anti-PD-1 antibody and IL-12. MVR-T3011 is being evaluated as monotherapy in patients with non-muscle invasive bladder cancer (NMIBC), including both BCG-unresponsive and BCG-naïve populations. Herein, we report the latest Phase II results of MVR-T3011 in BCG-unresponsive carcinoma in situ (CIS) and papillary NMIBC. Methods: In this ongoing trial, MVR-T3011 is administered intravesically in 50 mL without prewash. This simplified procedure utilizes the virus’s natural ability to bind to glycosaminoglycans (GAGs) on the urothelial surface as attachment receptors. Patients were assigned to two groups: 1) 2 × 10⁹ PFU, administered weekly for 12 weeks during the induction phase, followed by maintenance treatment every 2 weeks; 2) 1 × 10¹⁰ PFU, administered weekly for 6 weeks for induction, then every 3 weeks of treatment for maintenance. Both continued for up to 2 years. Efficacy was assessed every 3 months via cystoscopy, cytology, biopsy, and imaging. Primary endpoints were complete response rate (CRR) for CIS and recurrence-free survival (RFS) for papillary disease. The safety was fully evaluated. Results: As of Dec 31, 2025, a total of 43 patients were enrolled, 14 with CIS and 29 with Papillary. Among 13 evaluable CIS patients, 7 were treated at 2 × 10⁹ PFU dose level, achieving 6-month CRR of 71.4% (5/7), 3 patients maintained CR for 12 months, and 1 patient remained in CR for 18 months. 6 patients treated at 1 × 10¹⁰ PFU dose level, all achieved complete responses, with 100% CRR at 3 months (6/6), 6 months (5/5), and 9 months (3/3). Among 26 evaluable papillary patients, 16 were treated at the 2 × 10⁹ PFU dose level. The RFS rate was 80.8% (95% CI: 51.4–93.4) at 6 months, 74.0% (95% CI: 44.6–89.4) at both 12 and 15 months, and 64.8% (95% CI: 34.0–84.0) at both 18 and 21 months. 10 patients treated at 1 × 10¹⁰ PFU dose level, the 3-month and 6-month RFS rates were both 88.9%% (95% CI: 43.3–98.4). Assessment of the safety data revealed that most treatment-related adverse events (TRAEs) were grade 1. Common events included hematuria (25.0%), urinary tract infection (11.4%), proteinuria (9.1%), pollakiuria (6.8%), and rash (6.8%; immune-related). Only two grade 3 TRAEs were reported, both of which were urinary tract infections. No higher-grade TRAE or SAE occurred. Conclusions: MVR-T3011 is being evaluated as mono or combination therapy across multiple solid tumors. In this study, MVR-T3011 demonstrates suitability for intravesical administration, plus promising efficacy and a favorable safety profile. Durable complete responses were observed in CIS patients and encouraging 12-month RFS rates in papillary disease. These findings support its potential as a bladder-sparing option for BCG-unresponsive NMIBC. Clinical trial information: NCT06427291 .