1998P - Preliminary results from a phase I study of T3011, an oncolytic HSV expressing IL-12 and anti-PD-1 antibody, for BCG-failure non-muscle-invasive bladder cancer (NMIBC)

Background

BCG is the most effective intravesical therapy for patients with high-risk NMIBC. However, most patients become unresponsive to BCG and have recurrence within 1 year. Limited options are available for this population of patients. T3011 is a recombinant HSV-1 oncolytic virus expressing both IL-12 and anti-human PD-1 antibody. Upon delivery, locally produced IL-12 induces IFN-γ production, enhances the oncolytic activity of NK cells and cytotoxic T lymphocytes, promotes anti-angiogenesis, and inhibits tumor growth. Anti-PD-1 antibody acts as an immune checkpoint inhibitor to augment the tumor-killing activity of T-cells. Here, we present the preliminary results from a phase I study of T3011 in high risk NMIBC patients after BCG treatment failure.

Methods

In this open-label, dose-escalation phase I study, patients with BCG-failure high grade Ta, T1, or CIS +/- Ta/T1 were treated with T3011 via intravesical instillation. T3011 with three escalation cohorts (5×10⁷, 5×10⁸, 2×10⁹ PFU) were delivery in the entire solution volume of 50ml, QW in the first 12 weeks and then Q2W till 1 year. Safety was evaluated according to CTCAE5.0. Complete response (CR) was determined quarterly by combined negative results of cystoscopy/biopsy and urine UroVysion FISH testing.

Results

As of 18 Apr 2024, 13 pts were enrolled: 3 in Cohort 1 (5×10⁷ PFU), 3 in Cohort 2 (5×10⁸ PFU), and 7 in Cohort 3 (2×10⁹ PFU). The reported treatment related adverse events (TRAE) included hematuria (7.7%, 1/13), skin rash (7.7%, 1/13), vomiting (7.7%, 1/13) and pollakiuria (7.7%, 1/13). All TRAE were CTCAE grade 1. No DLT occurred. The maximum tolerated dose was not reached. The 3-month CR rate for all patients irrespective of dose levels was 60% (6/10). The CR rate was 33.3% (1/3) in 5×10⁷ PFU cohort, 66.7% (2/3) in 5×10⁸ PFU cohort, 75% (3/4) in 2×10⁹ PFU cohort. All responders at 3 months were able to continue to receive T3011 with median follow up 4.4 months, and 1 pt remained in CR at 6 months.

Conclusions

Intravesical T3011 demonstrates a promising anti-tumor efficacy and an excellent safety profile in patients with high risk BCG-failure NMIBC.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Fudan University Shanghai Cancer Center.

Funding

ImmVira Co. Ltd.

Disclosure

G. Zhou, K. Wang, R. Yan, X. Chen, X. Jin, W. Fu, J.J. Niu: Financial Interests, Institutional, Advisory Board: ImmVira Co. Ltd. All other authors have declared no conflicts of interest.