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

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...

Full description

Saved in:
Bibliographic Details
Main Authors: Lu Zhang, Shu Li, Jing Huang, Yan Wu, Liang Han, Tian Gao, Qingxia Fan, Suxia Luo, Binlei Liu, Lixin Zhou, Xinyu Wang, Ling Jia, Jianhua Shi, Zhichao Tan, Zhengfu Fan, Sijuan Ding, Chujie Bai, Ruifeng Xue, Jiayong Liu
Format: Article
Language:English
Published: BMJ Publishing Group 2025-01-01
Series:Journal for ImmunoTherapy of Cancer
Online Access:https://jitc.bmj.com/content/13/1/e010543.full
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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 This multicenter, phase 1/2 trial enrolled patients with injectable sarcoma lesions, who had failed at least 1 or more lines of standard treatment. Patients were treated with OH2 at three dose levels (106, 107 and 108 CCID50/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 with sarcoma. Further investigation of OH2 with HX008 in select sarcoma subtypes is warranted.
ISSN:2051-1426