Intratumoral oncolytic virus OH2 injection in patients with locally advanced or metastatic sarcoma: a phase 1/2 trial

作者：Zhichao Tan, Yan Wu, Zhengfu Fan, Tian Gao, Sijuan Ding, Liang Han, Suxia Luo, Qingxia Fan, Jianhua Shi, Chujie Bai, Ruifeng Xue, Shu Li, Lu Zhang, Xinyu Wang, Ling Jia, Lixin Zhou, Binlei Liu, Jing Huang, Jiao Liu · 发表于：Journal for ImmunoTherapy of Cancer · 年份：2025 · DOI：10.1136/jitc-2024-010543 · 被引用次数：13 · 研究领域：Virus-based gene therapy research、Cancer Research and Treatments、RNA Interference and Gene Delivery

BACKGROUND: Intratumoral oncolytic herpes simplex virus 2-GM CSF (OH2) injection has shown safety and antitumor efficacy in patients with solid tumors. Here, we examined the safety and efficacy of OH2 as a single agent or in combination with HX008, an NMPA-approved PD-1 inhibitor, in locally advanced or metastatic sarcoma patients. METHODS: /mL) as single agent or in combination with a fixed dose of HX008. The primary endpoints were safety and tolerability in phase 1 and objective response rate determined by RECIST (V.1.1) criteria and immune-RECIST in phase 2. RESULTS: Between October 20, 2020 and December 30, 2023, 26 patients were enrolled. Seven patients were treated with single-agent OH2 and 19 with HX008 and OH2 combination. No dose-limiting toxicities were observed during the dose escalation. We documented four partial or complete responses in injected lesions, and one partial response in non-injected lesions, which were all from the combination group. Hence, the overall response rate was 0% and 16.7% in the single agent and combination groups, respectively. The duration of response was 3.9-6.5 months. The most frequent treatment-related adverse events (TRAEs) were fever (n=9). Grade 3 or 4 TRAEs were reported in four patients (15.4%). A clear increase in CD8+cell density in the tumor microenvironment was observed in the patients' post-treatment specimens compared with baseline. CONCLUSIONS: Intratumoral injection of oncolytic virus OH2 is well tolerable in patients wi...