993MO - A phase I, open-label, multicenter, dose escalation safety and tolerability study of oncolytic virus OVV-01 in advanced solid tumors

Background

OVV-01 is a genetically engineered VSV oncolytic virus designed to selectively amplify in tumor cells and express tumor associated antigen NY-ESO-1. This study aims to harness the anti-tumor properties of VSV while simultaneously enhancing NY-ESO-1 expression in tumor cells and boosting the antigen-specific immune response.

Methods

This phase I, first-in-human, open-label, multicenter study was designed to evaluate the safety, tolerability, and efficacy of OVV-01 in patients with advanced solid tumors. OVV-01 was intratumorally injected biweekly (Q2W) 3 weeks after the first dose for a total of 6 doses. Dose escalation follows a 3+3 design at four doses of 3×10⁷ PFU, 3×10⁸ PFU, 3×10⁹ PFU, and 6×10¹⁰ PFU. The primary endpoints were safety and tolerability. The second endpoints included ORR and DCR of OVV-01, by investigators per RECIST 1.1.

Results

18 patients were enrolled into 4 dose groups, among them 6 were soft tissue sarcoma (STS). No dose-limiting toxicities were observed. Treatment-related adverse events (TRAEs) were observed in 94.4% (17/18) of patients (≥G3 33.3%). The most common TRAEs (≥20%) included pyrexia (66.7%), lymphocytopenia (27.8%), anemia (22.2%) and vomiting (22.2%). No treatment-related severe adverse events were observed. No viral shedding was detected by qPCR in patients’ saliva, urine, or stool. Based on the per-protocol set, 11 patients were evaluable for efficacy, and the ORR at 16 weeks (ORR_16w) was 27.3%, specifically: 0%, 33.3%, 25.0%, and 100% in the 3×10⁷ PFU, 3×10⁸ PFU, 3×10⁹ PFU and 6×10¹⁰ PFU dose groups. The DCR at 16 weeks (DCR_16w) was 63.6%. For doses above 3.0×10⁹ PFU, the ORR_16w was 40% (2/5), and the DCR_16w was 80% (4/5). Notably, among the four evaluable patients with advanced STS, the ORR_16w was 75%, and the DCR_16w was 75%. Two patients with STS achieved CR at doses above 3.0×10⁹ PFU. Overall PFS_24W rate was 43.1%.

Conclusions

The intratumor injection of OVV-01 was safe and well-tolerated in patients with advanced solid tumors, with no evidence of viral shedding. The efficacy of OVV-01 at dose levels higher than 3.0×10⁹ PFU was encouraging; A significant response was observed in patients with STS.

Clinical trial identification

NCT04787003.

Editorial acknowledgement

Legal entity responsible for the study

Joint Biosciences (SH) Ltd.

Funding

Joint Biosciences (SH) Ltd.

Disclosure

All authors have declared no conflicts of interest.