Background: There have been limited reports concerning treatment outcomes of oncolytic viruses in solid tumors other than melanoma. OH2 is a genetically engineered oncolytic herpes simplex virus type 2 designed to selectively amplify in tumor cells and express GM-CSF to enhance tumor-specific immune responses. Methods: We conducted an open-label, single-center, phase 1 study. Eligible pts were 18-75 years of age; had histologically confirmed advanced solid tumor; had progressed after standard systemic treatments. Pts were required to have tumor(s) deemed safe to inject, with a longest diameter of at least 0.5cm. Other eligibility criteria included measurable lesion as per RECIST v1.1; ECOGPS score of 0-1 and adequate organ functions. A 3+3 dose-escalation strategy was used in the study and 3 dose levels (10⁶, 10⁷ and 10⁸ CCID50/mL) of OH2 were assessed. OH2 was administered intratumorally every 3 weeks for the first cycle and every 2 weeks.Treatment may continue afterwards in ptswith potential clinical benefit at the discretion of the investigators. The primary objective was the safety and tolerability of OH2 injection as defined by the dose limiting toxicities (DLTs) within the first 3 weeks of therapy, and the maximum tolerated dose (MTD). Secondary objectives included efficacy and immunogenicity of OH2. Results: 11 pts were enrolled between April 17, 2019 and November 4, 2019. The median follow-up duration was 8.36 months (95%CI: 5.64-11.08). OH2 was well-tolerated as no DLTs were reported and no MTD reached. Before the end of the DLT assessment period,1 pt withdrew consent, and 1 pt died of arrhythmia unrelated to OH2, with negative OH2 DNA copies in serum, urine and saliva samples. Most treatment-related adverse events (TRAEs) observed were of grade 1-2, except that 1 pt in the 10⁸ CCID50/mL group developed grade 3 fever. The most common TRAEs were fever (n =5) and blood bilirubin level increase (n = 4). There were no grade 4 or 5 TRAEs. One pt(rectal cancer) had PR and 2 (appendix cancer and ovarian cancer) had SD as per RECIST v1.1. One patient (esophageal cancer) achieved iPR as per iRECIST criteria. The duration of follow-up for the 2 responders were 9.70 months and 8.36 months, respectively, and both had ongoing responses. Notably, regression of a non-injected lesion was observed in 1 patient. Conclusions: OH2 had a favorable safety profile with no DLTs and MTD. The dose expansion study in selected tumor types is currently underway. Clinical trial information: NCT03866525.