The investigator-initiated trial (IIT) of GO306 injection, a recombinant oncolytic vaccinia virus, in patients with advanced soft tissue sarcomas.

Abstract

11564 Background: Oncolytic vaccinia viruses exert anti-tumor effects via direct lysis and systemic immunity induction. Advanced soft tissue sarcomas (STS) are heterogeneous malignancies with limited post-standard therapy options. GO306 is a oncolytic virus expressing PD-1/TGFβ inhibitors for tumor-selective replication and enhanced immunity. We report GO306’s preliminary safety and tolerance in pretreated advanced STS. Methods: This open-label, single-arm IIT enrolled histologically confirmed advanced STS refractory to standard therapy. A 3+3 dose-escalation design was used, with intratumoral GO306 at 3×10 7 PFU, 3×10 8 PFU and 1×10 9 PFU. A 21-day DLT assessment period was set. Tumor assessment was done on day 28 per RECIST v1.1. Primary endpoints: MTD, DLTs, safety; secondary endpoints: OS, ORR, PFS, immunogenicity, viral shedding. Results: As of Dec 5 th , 2025, 10 participants were enrolled across 3 dose cohorts, 9 completed the 21-day DLT assessment (1 non-DLT withdrawal). Demographics: median age 52.4 years, 80% male, ECOG 1-2. No DLTs were observed; MTD not reached. A total of 110 AEs were reported, including 52 treatment-related adverse events (TRAEs), 98.8% (51/52) were grade 1-2, with 1 grade 3 pulmonary infection (SAE due to prolonged hospitalization). No grade 4-5 TRAEs occurred. Most common AEs: pyrexia (60%, grade 1-2), followed by hypokalemia, hypocalcemia and hypoalbuminemia (40% each, grade 1-2). Efficacy was evaluable in 8 participants: 87.5% (7/8) SD and 12.5% (1/8) PD. Survival data: 2 participants with OS＞5 months, 1 alive at 260 days (all received subsequent anti-tumor therapies), 2 with 90-day survival documented. Viral shedding: GO306 was below the limit of quantification (BLQ) in feces, urine, throat swabs, and plasma on day 3/7, undetectable on day 30 (some samples pending). PD-1 inhibitor was detectable in 6/10 participants (29.91~19073.64 ng/mL); TGFβ inhibitor in 7/10 participants (80.39 to 460.31 ng/ml). Conclusions: Intratumoral GO306 showed favorable safety profile and manageable TRAEs in pretreated advanced STS. Preliminary efficacy support phase I/II expansion and combination studies with other immunotherapies or targeted therapies. Clinical Trial Registration Number: ChiCTR2400088508. Xianhai Zhu and Hu Liu contributed equally as corresponding author. Clinical trial information: ChiCTR2400088508. Demographic and overall response of participants. Screen No. Age Gender ECOG Malignancy Diagnosis Overall Response* S002 60 M 1 Retroperitoneal Liposarcoma SD S003 59 F 2 Liposarcoma SD S006 70 M 1 Leiomyosarcoma SD S007 60 M 2 Retroperitoneal Liposarcoma PD S010 48 M 1 Retroperitoneal Leiomyosarcoma SD S011 48 M 1 Retroperitoneal Leiomyosarcoma SD S012 56 M 1 Chondrosarcoma SD S013 30 M 1 Synovial Sarcoma SD Abbreviations: *Per RECIST V1.1; 8/10 enrolled participants had evaluable day-28 tumor assessments and are included.