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...
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BMJ Publishing Group
2025-01-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/13/1/e010543.full |
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| author | 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 |
| author_facet | 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 |
| author_sort | Lu Zhang |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-a0654617a7fb423db397de4932d88024 |
| institution | Kabale University |
| issn | 2051-1426 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMJ Publishing Group |
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| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-a0654617a7fb423db397de4932d880242025-01-18T04:30:09ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262025-01-0113110.1136/jitc-2024-010543Intratumoral oncolytic virus OH2 injection in patients with locally advanced or metastatic sarcoma: a phase 1/2 trialLu Zhang0Shu Li1Jing Huang2Yan Wu3Liang Han4Tian Gao5Qingxia Fan6Suxia Luo7Binlei Liu8Lixin Zhou9Xinyu Wang10Ling Jia11Jianhua Shi12Zhichao Tan13Zhengfu Fan14Sijuan Ding15Chujie Bai16Ruifeng Xue17Jiayong Liu18Department of Bone and Soft Tissue Sarcoma, Peking University Cancer Hospital. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Beijing, ChinaDepartment of Bone and Soft Tissue Sarcoma, Peking University Cancer Hospital. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Beijing, ChinaDepartment of Medical Oncology, Peking Union Medical College, Beijing, ChinaDepartment of Pathology, Peking University Cancer Hospital. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Beijing, ChinaDepartment of Oncology, Xuzhou Central Hospital, Xuzhou, Jiangsu, ChinaDepartment of Bone and Soft Tissue Tumor, Peking University Cancer Hospital. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Beijing, ChinaDepartment of Oncology, Zhengzhou University First Affiliated Hospital, Zhengzhou, Henan, ChinaThe Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan, ChinaWuhan Binhui Biopharmaceutical Co Ltd, Wuhan, Hubei, ChinaDepartment of Pathology, Peking University Cancer Hospital. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Beijing, ChinaDepartment of Bone and Soft Tissue Tumor, Peking University Cancer Hospital. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Beijing, ChinaDepartment of Pathology, Peking University Cancer Hospital. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Beijing, ChinaDepartment of Oncology, Linyi Cancer Hospital, Linyi, Shandong, ChinaDepartment of Bone and Soft Tissue Sarcoma, Peking University Cancer Hospital. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Beijing, ChinaDepartment of Bone and Soft Tissue Tumor, Peking University Cancer Hospital. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Beijing, ChinaThe Center Hospital of Yongzhou, Yongzhou, Hunan, ChinaDepartment of Bone and Soft Tissue Sarcoma, Peking University Cancer Hospital. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Beijing, ChinaDepartment of Bone and Soft Tissue Sarcoma, Peking University Cancer Hospital. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Beijing, ChinaDepartment of Bone and Soft Tissue Tumor, Peking University Cancer Hospital. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Beijing, ChinaBackground 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.https://jitc.bmj.com/content/13/1/e010543.full |
| spellingShingle | 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 Intratumoral oncolytic virus OH2 injection in patients with locally advanced or metastatic sarcoma: a phase 1/2 trial Journal for ImmunoTherapy of Cancer |
| title | Intratumoral oncolytic virus OH2 injection in patients with locally advanced or metastatic sarcoma: a phase 1/2 trial |
| title_full | Intratumoral oncolytic virus OH2 injection in patients with locally advanced or metastatic sarcoma: a phase 1/2 trial |
| title_fullStr | Intratumoral oncolytic virus OH2 injection in patients with locally advanced or metastatic sarcoma: a phase 1/2 trial |
| title_full_unstemmed | Intratumoral oncolytic virus OH2 injection in patients with locally advanced or metastatic sarcoma: a phase 1/2 trial |
| title_short | Intratumoral oncolytic virus OH2 injection in patients with locally advanced or metastatic sarcoma: a phase 1/2 trial |
| title_sort | intratumoral oncolytic virus oh2 injection in patients with locally advanced or metastatic sarcoma a phase 1 2 trial |
| url | https://jitc.bmj.com/content/13/1/e010543.full |
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