Novel Immunotherapy Achieves Responses/RFS in High-Risk, BCG-Unresponsive NMIBC

Updated interim results for Herpes Virus T3011 injection (MVR-T3011), an HSV-1-based oncolytic immunotherapy, as a treatment for patients with high-risk, Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) from a phase 1/2a trial (NCT06971614) were recently shared at the 26th Annual Meeting of the Society of Urologic Oncology.^1,2

Among the 16 evaluable patients with BCG-unresponsive papillary disease who received MVR-T3011 at 2 x 109 plaque-forming units (PFU), the recurrence-free survival (RFS) was 87.1% at 3 months, 80.4% at 6 months, 80.4% at 9 months, and 71.4% at 12 months. Of the 6 evaluable patients in this population who received MVR-T3011 at 1 x 1010 PFU, the RFS was 100% at both 3 months and 6 months.

Further, of 7 evaluable patients with BCG-unresponsive carcinoma in situ (CIS) with or without Ta/T1 who received MVR-T3011 at 2 x 109 PFU, the complete response (CR) rate at any time, the 3-month CR rate, and the 6-month CR rate were all 71.4%. Of 5 evaluable patients with the same characteristics who received MVR-T3011 at a different dose—1 x 1010 PFU—the CR at any time rate, the 3-month CR rate, and the 6-month CR rate were all 100%.

"We are highly encouraged by the interim efficacy data from the study, especially the high CR and RFS rate for both BCG-unresponsive CIS and papillary patients at 1x1010 PFU," stated Dr Grace Zhou, chairwoman and chief executive officer of ImmVira, in a press release.¹ "We have initiated a phase 2 trial for BCG-unresponsive high-risk NMIBC in the US in June 2025 and are progressing a global multi-regional clinical trial inclusive of China. We believe MVR-T3011 could emerge as the new generation of therapy for patients with high-risk, BCG-unresponsive NMIBC."

A total of 26 patients with papillary disease were enrolled in the trial, 16 and 10 of whom, respectively, were treated with intravesical MVR-T3011 at 2x109 PFU and 1x1010 PFU; 12 patients with CIS were enrolled, 7 and 5 of whom were treated at 2x109 PFU and 1x1010 PFU, respectively.

Eligible patients in the trial were 18 years or older with histologically confirmed diagnosis of NMIBC that was stage Ta, T1, and/or Cis. Additional enrollment criteria include having all toxicities caused by other treatments recovered to grade 1 or lower, an ECOG performance status from 0 to 2, an expected survival of at least 24 weeks, and sufficient laboratory test values.

Exclusion criteria included concurrent or prior history of muscle-invasive or metastatic bladder cancer; urothelial carcinoma of the upper genitourinary tract or prostatic urethra within 24 months of study; receipt of chemotherapy, biotherapy, endocrine therapy, or any other anti-neoplastic therapies within 4 weeks of study; receipt of radiotherapy within 2 weeks of study; history of brain metastases; concurrent or prior history of other malignancies; and previous treatment with oncolytic virus.

The primary end points of the trial included CR rate, RFS, incidence of grade 3 or higher treatment-related adverse events (TRAEs), and incidence of TRAEs leading to treatment discontinuation, dose modification, or treatment interruption.

Regarding safety, MVR-T3011 achieved a favorable safety and tolerability profile, with the majority of treatment-emergent adverse events (TEAEs) being grade 1 or 2. A total of 5 grade 3 TEAEs were reported in the trial, of which 2 were TRAEs that were consistent with commonly associated reactions to catheterization procedures. No dose-limiting toxicities occurred during the trial.

MVR-T3011 utilizes a proprietary “3-in-1” design that unites a tumor-lytic HSV-1 backbone with anti–PD-(L)1 antibody and interleukin-12. This design enables the agent to simultaneously stimulate innate and adaptive immunity and lyse tumor cells.

References

1. Ye D, Wu J, Zhang M, et al. Intravesical T3011, an IL-12/Anti-PD-1 armed oncolytic HSV-1, in BCG-unresponsive high-risk NMIBC: A phase I/IIa trial. Presented at the 26th Annual Meeting of the Society of Urologic Oncology; December 2-5, 2025; Phoenix, AZ.
2. High response in bladder cancer: Immvira announced its MVR-T3011 latest clinical results in BCG-unresponsive bladder cancer patients at 2025 Annual Meeting of the Society of Urologic Oncology. News release. ImmVira. December 3, 2025. Accessed December 4, 2025. https://tinyurl.com/4nxy7569
3. A study of T3011 in patients with BCG-unresponsive NMIBC or BCG-exposed, chemotherapy-unresponsive NMIBC. ClinicalTrials.gov. Updated July 23, 2025. Accessed December 4, 2025. https://tinyurl.com/ms8mzekw