ONCOS-102 plus pemetrexed and platinum chemotherapy in malignant pleural mesothelioma: a randomized phase 2 study investigating clinical outcomes and the tumor microenvironment
Background ONCOS-102, an oncolytic adenovirus expressing granulocyte-macrophage colony-stimulating factor, can alter the tumor microenvironment to an immunostimulatory state. Combining ONCOS-102 with standard-of-care chemotherapy for malignant pleural mesothelioma (MPM) may improve treatment outcome...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMJ Publishing Group
2023-09-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/11/9/e007552.full |
| _version_ | 1797666989212172288 |
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| author | Magnus Jaderberg Victor Levitsky Luis Paz-Ares Nicolas Isambert Susana Cedres Xavier Serres Charles Ricordel Sylvia Vetrhus Alex Martinez-Marti Santiago Viteri Alejandro Navarro Jon Zugazagoitia Santiago Ponce Mercedes Herrera-Juarez Mathieu Lederlin Thomas Birkballe Hansen |
| author_facet | Magnus Jaderberg Victor Levitsky Luis Paz-Ares Nicolas Isambert Susana Cedres Xavier Serres Charles Ricordel Sylvia Vetrhus Alex Martinez-Marti Santiago Viteri Alejandro Navarro Jon Zugazagoitia Santiago Ponce Mercedes Herrera-Juarez Mathieu Lederlin Thomas Birkballe Hansen |
| author_sort | Magnus Jaderberg |
| collection | DOAJ |
| description | Background ONCOS-102, an oncolytic adenovirus expressing granulocyte-macrophage colony-stimulating factor, can alter the tumor microenvironment to an immunostimulatory state. Combining ONCOS-102 with standard-of-care chemotherapy for malignant pleural mesothelioma (MPM) may improve treatment outcomes.Methods In this open-label, randomized study, patients with unresectable MPM received intratumoral ONCOS-102 (3×1011 virus particles on days 1, 4, 8, 36, 78, and 120) and pemetrexed plus cisplatin/carboplatin (from day 22), or pemetrexed plus cisplatin/carboplatin alone. The primary endpoint was safety. Overall survival (OS), progression-free survival, objective response rate, and tumor immunologic activation (baseline and day 36 biopsies) were also assessed.Results In total, 31 patients (safety lead-in: n=6, randomized: n=25) were enrolled. Anemia (15.0% and 27.3%) and neutropenia (40.0% and 45.5%) were the most frequent grade ≥3 adverse events (AEs) in the ONCOS-102 (n=20) and chemotherapy-alone (n=11) cohorts. No patients discontinued ONCOS-102 due to AEs. No statistically significant difference in efficacy endpoints was observed. There was a numerical improvement in OS (30-month OS rate 34.1% vs 0; median OS 20.3 vs 13.5 months) with ONCOS-102 versus chemotherapy alone in chemotherapy-naïve patients (n=17). By day 36, ONCOS-102 was associated with increased T-cell infiltration and immune-related gene expression that was not observed in the control cohort. Substantial immune activation in the tumor microenvironment was associated with survival at month 18 in the ONCOS-102 cohort.Conclusions ONCOS-102 plus pemetrexed and cisplatin/carboplatin was well tolerated by patients with MPM. In injected tumors, ONCOS-102 promoted a proinflammatory environment, including T-cell infiltration, which showed association with survival at month 18. |
| first_indexed | 2024-03-11T20:06:39Z |
| format | Article |
| id | doaj.art-948af889fc44483eac5e19bcc3f77280 |
| institution | Directory Open Access Journal |
| issn | 2051-1426 |
| language | English |
| last_indexed | 2024-03-11T20:06:39Z |
| publishDate | 2023-09-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj.art-948af889fc44483eac5e19bcc3f772802023-10-03T13:55:08ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262023-09-0111910.1136/jitc-2023-007552ONCOS-102 plus pemetrexed and platinum chemotherapy in malignant pleural mesothelioma: a randomized phase 2 study investigating clinical outcomes and the tumor microenvironmentMagnus Jaderberg0Victor Levitsky1Luis Paz-Ares2Nicolas Isambert3Susana Cedres4Xavier Serres5Charles Ricordel6Sylvia Vetrhus7Alex Martinez-Marti8Santiago Viteri9Alejandro Navarro10Jon Zugazagoitia11Santiago Ponce12Mercedes Herrera-Juarez13Mathieu Lederlin14Thomas Birkballe Hansen1510 Research and Development, Circio Holding ASA, Oslo, Norway10 Research and Development, Circio Holding ASA, Oslo, Norway1 Department of Medical Oncology, Hospital Universitario 12 de Octubre, Madrid, Spain5 Centre Georges-François Leclerc, Dijon, France2 Department of Medical Oncology, Vall d`Hebron University Hospital, Barcelona, Spain2 Department of Medical Oncology, Vall d`Hebron University Hospital, Barcelona, Spain4 Department of Pulmonology, Centre Hospitalier Universitaire de Rennes, Rennes, France10 Research and Development, Circio Holding ASA, Oslo, Norway2 Department of Medical Oncology, Vall d`Hebron University Hospital, Barcelona, Spain6 Department of Medical Oncology, Instituto Oncológico Rosell, Grupo Quironsalud, Hospital Universitario Dexeus, Barcelona, Spain2 Department of Medical Oncology, Vall d`Hebron University Hospital, Barcelona, Spain1 Department of Medical Oncology, Hospital Universitario 12 de Octubre, Madrid, Spain1 Department of Medical Oncology, Hospital Universitario 12 de Octubre, Madrid, Spain1 Department of Medical Oncology, Hospital Universitario 12 de Octubre, Madrid, Spain7 Department of Radiology, Centre Hospitalier Universitaire de Rennes, Rennes, France10 Research and Development, Circio Holding ASA, Oslo, NorwayBackground ONCOS-102, an oncolytic adenovirus expressing granulocyte-macrophage colony-stimulating factor, can alter the tumor microenvironment to an immunostimulatory state. Combining ONCOS-102 with standard-of-care chemotherapy for malignant pleural mesothelioma (MPM) may improve treatment outcomes.Methods In this open-label, randomized study, patients with unresectable MPM received intratumoral ONCOS-102 (3×1011 virus particles on days 1, 4, 8, 36, 78, and 120) and pemetrexed plus cisplatin/carboplatin (from day 22), or pemetrexed plus cisplatin/carboplatin alone. The primary endpoint was safety. Overall survival (OS), progression-free survival, objective response rate, and tumor immunologic activation (baseline and day 36 biopsies) were also assessed.Results In total, 31 patients (safety lead-in: n=6, randomized: n=25) were enrolled. Anemia (15.0% and 27.3%) and neutropenia (40.0% and 45.5%) were the most frequent grade ≥3 adverse events (AEs) in the ONCOS-102 (n=20) and chemotherapy-alone (n=11) cohorts. No patients discontinued ONCOS-102 due to AEs. No statistically significant difference in efficacy endpoints was observed. There was a numerical improvement in OS (30-month OS rate 34.1% vs 0; median OS 20.3 vs 13.5 months) with ONCOS-102 versus chemotherapy alone in chemotherapy-naïve patients (n=17). By day 36, ONCOS-102 was associated with increased T-cell infiltration and immune-related gene expression that was not observed in the control cohort. Substantial immune activation in the tumor microenvironment was associated with survival at month 18 in the ONCOS-102 cohort.Conclusions ONCOS-102 plus pemetrexed and cisplatin/carboplatin was well tolerated by patients with MPM. In injected tumors, ONCOS-102 promoted a proinflammatory environment, including T-cell infiltration, which showed association with survival at month 18.https://jitc.bmj.com/content/11/9/e007552.full |
| spellingShingle | Magnus Jaderberg Victor Levitsky Luis Paz-Ares Nicolas Isambert Susana Cedres Xavier Serres Charles Ricordel Sylvia Vetrhus Alex Martinez-Marti Santiago Viteri Alejandro Navarro Jon Zugazagoitia Santiago Ponce Mercedes Herrera-Juarez Mathieu Lederlin Thomas Birkballe Hansen ONCOS-102 plus pemetrexed and platinum chemotherapy in malignant pleural mesothelioma: a randomized phase 2 study investigating clinical outcomes and the tumor microenvironment Journal for ImmunoTherapy of Cancer |
| title | ONCOS-102 plus pemetrexed and platinum chemotherapy in malignant pleural mesothelioma: a randomized phase 2 study investigating clinical outcomes and the tumor microenvironment |
| title_full | ONCOS-102 plus pemetrexed and platinum chemotherapy in malignant pleural mesothelioma: a randomized phase 2 study investigating clinical outcomes and the tumor microenvironment |
| title_fullStr | ONCOS-102 plus pemetrexed and platinum chemotherapy in malignant pleural mesothelioma: a randomized phase 2 study investigating clinical outcomes and the tumor microenvironment |
| title_full_unstemmed | ONCOS-102 plus pemetrexed and platinum chemotherapy in malignant pleural mesothelioma: a randomized phase 2 study investigating clinical outcomes and the tumor microenvironment |
| title_short | ONCOS-102 plus pemetrexed and platinum chemotherapy in malignant pleural mesothelioma: a randomized phase 2 study investigating clinical outcomes and the tumor microenvironment |
| title_sort | oncos 102 plus pemetrexed and platinum chemotherapy in malignant pleural mesothelioma a randomized phase 2 study investigating clinical outcomes and the tumor microenvironment |
| url | https://jitc.bmj.com/content/11/9/e007552.full |
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