Randomized phase 2 trial of intravenous oncolytic virus JX-594 combined with low-dose cyclophosphamide in patients with advanced soft-tissue sarcoma
Abstract JX-594 is an oncolytic vaccinia virus genetically modified to replicate selectively in tumor cells. Metronomic chemotherapy has shown preclinical synergy with oncolytic viruses. We report here the results of the METROMAJX which is a randomized phase II clinical trial investigating the combi...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-10-01
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| Series: | Journal of Hematology & Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13045-022-01370-9 |
| _version_ | 1798029068486049792 |
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| author | Maud Toulmonde Sophie Cousin Michèle Kind Jean-Philippe Guegan Alban Bessede Francois Le Loarer Raul Perret Coralie Cantarel Carine Bellera Antoine Italiano |
| author_facet | Maud Toulmonde Sophie Cousin Michèle Kind Jean-Philippe Guegan Alban Bessede Francois Le Loarer Raul Perret Coralie Cantarel Carine Bellera Antoine Italiano |
| author_sort | Maud Toulmonde |
| collection | DOAJ |
| description | Abstract JX-594 is an oncolytic vaccinia virus genetically modified to replicate selectively in tumor cells. Metronomic chemotherapy has shown preclinical synergy with oncolytic viruses. We report here the results of the METROMAJX which is a randomized phase II clinical trial investigating the combination of JX-594 combined with metronomic cyclophosphamide (arm 1) or metronomic cyclophosphamide (arm 2) in patients with advanced STS. A two-stage Simon design was used. JX-594 was administered intra-venously at the dose 1.109 every 2 weeks for the first 3 injections and then every 3 weeks. Cyclophosphamide was given orally at the dose of 50 mg BID 1 week on 1 week off. The primary endpoint was the 6-month non progression rate. 20 patients were included (arm 1:15, arm 2:5). The two most frequent toxicities were grade 1 fatigue and fever and grade 2 fatigue and grade 2 lymphopenia in arms 1 and 2, respectively. In arm 1, 12 patients were assessable for the efficacy analysis. None of them were progression-free at 6 months indicating that the first stage of the Simon's design was not satisfied. One patient out 4 assessable for efficacy was progression-free at 6 months in arm 2. High throughput analysis of sequential plasma samples revealed an upregulation of protein biomarkers reflecting immune induction such as CXCL10 and soluble CD8 antigen in arm 1. Systemic treatment with JX-594 is safe in patients with advanced STS. Further investigations are needed to improve immune response to oncolytic viruses and define their therapeutic potential in patients with STS. |
| first_indexed | 2024-04-11T19:19:25Z |
| format | Article |
| id | doaj.art-ec83622d8f95479e967a29f33eed7e35 |
| institution | Directory Open Access Journal |
| issn | 1756-8722 |
| language | English |
| last_indexed | 2024-04-11T19:19:25Z |
| publishDate | 2022-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Hematology & Oncology |
| spelling | doaj.art-ec83622d8f95479e967a29f33eed7e352022-12-22T04:07:21ZengBMCJournal of Hematology & Oncology1756-87222022-10-011511510.1186/s13045-022-01370-9Randomized phase 2 trial of intravenous oncolytic virus JX-594 combined with low-dose cyclophosphamide in patients with advanced soft-tissue sarcomaMaud Toulmonde0Sophie Cousin1Michèle Kind2Jean-Philippe Guegan3Alban Bessede4Francois Le Loarer5Raul Perret6Coralie Cantarel7Carine Bellera8Antoine Italiano9Early Phase Trials and Sarcoma Units, Department of Medical Oncology, Institut BergoniéEarly Phase Trials and Sarcoma Units, Department of Medical Oncology, Institut BergoniéDepartment of Medical Imaging, Institut BergoniéExplicyteExplicyteDepartment of Pathology, Institut BergoniéDepartment of Pathology, Institut BergoniéInserm, Bordeaux Population Health Research Center, Epicene Team, UMR 1219, Univ. BordeauxInserm, Bordeaux Population Health Research Center, Epicene Team, UMR 1219, Univ. BordeauxEarly Phase Trials and Sarcoma Units, Department of Medical Oncology, Institut BergoniéAbstract JX-594 is an oncolytic vaccinia virus genetically modified to replicate selectively in tumor cells. Metronomic chemotherapy has shown preclinical synergy with oncolytic viruses. We report here the results of the METROMAJX which is a randomized phase II clinical trial investigating the combination of JX-594 combined with metronomic cyclophosphamide (arm 1) or metronomic cyclophosphamide (arm 2) in patients with advanced STS. A two-stage Simon design was used. JX-594 was administered intra-venously at the dose 1.109 every 2 weeks for the first 3 injections and then every 3 weeks. Cyclophosphamide was given orally at the dose of 50 mg BID 1 week on 1 week off. The primary endpoint was the 6-month non progression rate. 20 patients were included (arm 1:15, arm 2:5). The two most frequent toxicities were grade 1 fatigue and fever and grade 2 fatigue and grade 2 lymphopenia in arms 1 and 2, respectively. In arm 1, 12 patients were assessable for the efficacy analysis. None of them were progression-free at 6 months indicating that the first stage of the Simon's design was not satisfied. One patient out 4 assessable for efficacy was progression-free at 6 months in arm 2. High throughput analysis of sequential plasma samples revealed an upregulation of protein biomarkers reflecting immune induction such as CXCL10 and soluble CD8 antigen in arm 1. Systemic treatment with JX-594 is safe in patients with advanced STS. Further investigations are needed to improve immune response to oncolytic viruses and define their therapeutic potential in patients with STS.https://doi.org/10.1186/s13045-022-01370-9Soft-tissue sarcomaVirus oncolyticsJX-594Low-dose cyclophosphamide |
| spellingShingle | Maud Toulmonde Sophie Cousin Michèle Kind Jean-Philippe Guegan Alban Bessede Francois Le Loarer Raul Perret Coralie Cantarel Carine Bellera Antoine Italiano Randomized phase 2 trial of intravenous oncolytic virus JX-594 combined with low-dose cyclophosphamide in patients with advanced soft-tissue sarcoma Journal of Hematology & Oncology Soft-tissue sarcoma Virus oncolytics JX-594 Low-dose cyclophosphamide |
| title | Randomized phase 2 trial of intravenous oncolytic virus JX-594 combined with low-dose cyclophosphamide in patients with advanced soft-tissue sarcoma |
| title_full | Randomized phase 2 trial of intravenous oncolytic virus JX-594 combined with low-dose cyclophosphamide in patients with advanced soft-tissue sarcoma |
| title_fullStr | Randomized phase 2 trial of intravenous oncolytic virus JX-594 combined with low-dose cyclophosphamide in patients with advanced soft-tissue sarcoma |
| title_full_unstemmed | Randomized phase 2 trial of intravenous oncolytic virus JX-594 combined with low-dose cyclophosphamide in patients with advanced soft-tissue sarcoma |
| title_short | Randomized phase 2 trial of intravenous oncolytic virus JX-594 combined with low-dose cyclophosphamide in patients with advanced soft-tissue sarcoma |
| title_sort | randomized phase 2 trial of intravenous oncolytic virus jx 594 combined with low dose cyclophosphamide in patients with advanced soft tissue sarcoma |
| topic | Soft-tissue sarcoma Virus oncolytics JX-594 Low-dose cyclophosphamide |
| url | https://doi.org/10.1186/s13045-022-01370-9 |
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