Phase 1, open-label, multicenter, dose escalation safety and tolerability study of oncolytic virus OVV-01 in advanced solid tumors.

Abstract

Background: OVV-01 is a genetically engineered vesicular stomatitis virus oncolytic virus designed to selectively amplify in tumor cells and express tumor-associated antigen NY-ESO-1. This study was designed to evaluate the safety, tolerability, and efficacy of OVV-01 in patients with advanced solid tumors.

Methods: This is a phase 1, first-in-human, open-label, multicenter study of OVV-01 in patients with advanced solid tumors. OVV-01 was intratumorally injected biweekly (every two weeks, Q2W), 3 weeks after the first dose for a total of six doses. Dose escalation follows a 3+3 design at four doses of 6×10⁷ Plaue-Forming Unit (PFU), 6×10⁸ PFU, 6×10⁹ PFU, and 1.2×10¹¹ PFU. The primary endpoints were safety and tolerability. The second endpoints included overall response rate (ORR) and disease control rate (DCR) of OVV-01, by investigators per Response Evaluation Criteria in Solid Tumors V.1.1.

Results: 18 patients were enrolled into four dose groups, among whom 6 were soft tissue sarcoma (STS). No dose-limiting toxicities and treatment-related severe adverse events were observed. 11 patients were evaluated for efficacy, and the ORR was 27.3%, and the DCR was 63.6%. Among the four evaluable patients with advanced STS, the ORR was 75%. Two patients with STS achieved CR at doses above 6.0×10⁹ PFU.

Conclusions: The intratumor injection of OVV-01 was safe and well-tolerated in patients with advanced solid tumors. A significant response was observed in patients with STS.

Trial registration number: NCT04787003.