(P 48) A SINGLE-ARM, OPEN-LABEL CLINICAL STUDY OF OVV-01 ONCOLYTIC VIRUS INJECTION AS MONOTHERAPY OR IN COMBINATION WITH IMMUNE CHECKPOINT INHIBITORS FOR ADVANCED SOLID TUMOR PATIENTS

Objective: The oncolytic virus is a type of virus that originates from natural or genetically modified or engineered viruses, and it is a multifunctional novel therapeutic drug. Common oncolytic viruses include mutated adenovirus ONYX-015 (dl1520), HSV-1 mutant G207, human retrovirus 3, vesicular stomatitis virus (VSV), and Epstein-Barr virus (EBV). It is also known as conditionally replicating virus or selectively replicating virus, which can selectively infect tumor cells and replicate within them, ultimately lysing and killing the tumor cells. It then releases progeny viral particles to further infect surrounding tumor cells without replication or cytotoxicity in normal tissue cells. Moreover, it can induce specific anti-tumor immune responses, providing promising prospects for immunotherapy of tumors.
VSV can express a variety of cell surface molecules, including low-density lipoprotein receptor, phosphatidylserine, salivary glycolipids, and heparan sulfate. VSV can attach to the cell surface through these molecules. Its characteristics include fast replication and trans-synaptic spread, as well as extremely high levels of exogenous gene expression. Compared to other oncolytic virus platforms currently under development, VSV has a small genome size and is easy to manipulate; it has a shorter replication time and an independent cell cycle; it can rapidly grow in a wide range of cell lines with high titers, allowing for large-scale production; there is no risk of transformation during cytoplasmic replication in host cells. This oncolytic virus does not integrate into DNA and can be modified to avoid neuroinflammation caused by wild-type viruses.

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 (pts) with advanced solid tumors. OVV-01 Injection 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 dose levels ranging from 3.0×107 PFU to 6.0×1010 PFU. The primary endpoints were safety and tolerability. The second endpoints included evaluating the efficacy of OVV-01 by investigators per RECIST 1.1.

Results: OVV-01 injection was generally safe and well tolerated with no DLT events in all dose groups. Dose escalation stage, ORR16w is 27.3%, ORR8w is 0, ORR24w is 27.3%, DCR24w was 63.6%, PFSR24w is 43.08%, the median DoR24w for NA, the median overall survival for NA. The subjects accept after dosing immunogenicity were positive for all subjects. Live virions were only detected in peripheral blood (serum) of some subjects at 0.25h, 1h, 3h, 12h, and 24h after the study drug administration, but not in saliva, urine, and feces. Subjects after accepting study drug dosage, were not detected in the whole blood (plasma) live virus particles.

Conclusion: Oncolytic virus has a certain therapeutic effect on bone and soft tissue sarcoma, but more clinical data are still lacking. According to the current results, oncolytic virus therapy can be clinically beneficial for patients with bone and soft tissue tumors.