Introduction:

Radical cystectomy (RC) remains the standard treatment for high-risk (HR) non-muscle-invasive bladder cancer (NMIBC) patients who experience recurrence after Bacillus Calmette–Guérin (BCG) therapy, particularly those classified as BCG-unresponsive. Although effective, RC is associated with significant morbidity, underscoring the urgent need for effective bladder-preserving alternatives.  Herpes Virus T3011 Injection (MVR-T3011) is a clinical-stage oncolytic herpes simplex virus type 1 (HSV-1) designed for cancer immunotherapy. Genetically engineered for tumor-selective replication, it delivers localized expression of two potent immunomodulators: interleukin-12 (IL-12) and an anti–PD-1 antibody. This dual mechanism combines direct oncolysis through viral replication with in situ immune activation, enhancing both local and systemic antitumor immune responses. This study aims to evaluate the efficacy and safety of intravesical T3011 instillation in HR NMIBC patients with BCG failure.

Methods:

BCG-unresponsive NMIBC patients were enrolled and treated with intravesical MVR-T3011 at two dose levels: 2.0×10⁹ PFU and 1.0×10¹⁰ PFU in a 50 mL solution. To streamline administration, no bladder prewash was performed. At 2.0×10⁹ PFU dose level, MVR-T3011 is administered once a week (QW) for 12 weeks in induction course and once every 2 weeks (Q2W) for 1 year, then once every 3 weeks (Q3W) until 2 years in maintenance course. At 1.0×10¹⁰ PFU dose level, MVR-T3011 is administered QW for 6 weeks in induction course (with a second induction allowed, if applicable) and Q3W until 2 years in maintenance course. Patients will be evaluated for recurrence and progression using cystoscopy, cytology, biopsy (if applicable), and CT/MRI (if applicable). The primary efficacy endpoints were complete response (CR) rate in patients with carcinoma in situ (CIS) and 12-month RFS in Ta/T1 without CIS patients.

Results:

As of July 11, sixteen efficacy-evaluable pts with papillary Ta/T1 without CIS received MVR-T3011 at 2.0×10⁹ PFU. The 6- and 12-month RFS rates were 80.4% (95% CI: 50.6–93.2) and 71.4% (95% CI: 39.8–88.4), respectively. Among 7 efficacy-evaluable patients with CIS at the same dose level, the CR rate was 71.4% (5/7) and remained durable through 6 months. At the 1.0×10¹⁰ PFU dose level, all 3 efficacy-evaluable CIS patients achieved CR at 3 months (100%, 3/3). Overall, the 3-month CR rate was 80% (8/10) in evaluable CIS patients across both dose levels. Most treatment-related adverse events (TRAEs) were grade 1, including haematuria (23.4%), urinary tract infection (8.5%), rash (8.5%), proteinuria (8.5%), pollakiuria (4.3%), micturition urgency (2.1%), vomiting (2.1%), and dry mouth (2.1%). Urinary tract infections included grade 2 and 3 events. No grade 4 or 5 TRAEs or treatment-related serious adverse events (SAEs) were reported.

Conclusion:

With durable complete responses in CIS patients and encouraging 12-month RFS rates in Ta/T1 disease, MVR-T3011 shows potential as an effective bladder-sparing therapy for BCG-failure NMIBC, supported by its manageable safety profile.

Funding: N/A