Intravesical T3011, an IL-12/anti-PD-1 armed oncolytic HSV-1, in BCG-naïve high-risk NMIBC: A phase IIa trial.

762 Background: Intravesical BCG is the standard of care for BCG-naïve high-risk non-muscle-invasive bladder cancer (NMIBC) patients. However, the scarcity of BCG products is a global issue, and coupled with the side effects of BCG therapy itself, approximately 30-40% of patients fail to receive effective BCG treatment. Therefore, it is essential to seek better alternative therapies to BCG in order to meet clinical needs. Herpes Virus T3011 Injection (MVR-T3011) is a clinical-stage oncolytic herpes simplex virus type 1 (HSV-1) developed for cancer immunotherapy. Genetically engineered to replicate selectively in tumors, it enables localized expression of two potent immunomodulators: interleukin-12 (IL-12) and an anti-PD-1 antibody. This study is designed to assess the efficacy and safety of intravesical T3011 in BCG-naïve high-risk NMIBC patients. Methods: BCG-naïve 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. MVR-T3011 was administered QW for 6 weeks in the induction course (with a second induction allowed, if applicable) and Q3W until 2 years in the maintenance course. Patients will be evaluated for recurrence and progression using cystoscopy, cytology, biopsy (if applicable), and CT/MRI (if applicable). The primary efficacy endpoint was 12-month RFS in papillary Ta/T1 without CIS patients. Results: As of October 10, 2025, 16 patients with papillary Ta/T1 have been treated with MVR-T3011 monotherapy (3 received 2×10 9 PFU dose and 13 received 1×10 10 PFU dose), with 8 assessments completed. In the efficacy-evaluable patients, the 3-month (n = 8), 6-month (n = 5), 9-month (n = 3), 12-month(n = 1), and 15-month (n = 1) RFS rates were all 100% respectively. No grade 3 or above TEAEs or SAEs were reported. Grade 1-2 TEAEs included dysuria, hematuria, urinary tract infection, dry mouth, alanine aminotransferase increased, hyperuricemia, breast fibroadenoma, and aspartate aminotransferase increased. Treatment-related adverse events (TRAEs) included urinary tract infection and dry mouth. Conclusions: Oncolytic viruses and BCG both fall within the realm of immunotherapy, with the former possessing scientific attributes to potentially replace BCG in the future. With encouraging preliminary efficacy in papillary Ta/T1 disease, MVR-T3011 shows potential as an effective alternative therapy for BCG-naïve NMIBC, supported by its favorable safety profile.