{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T01:14:06Z","timestamp":1791335646008,"version":"4.3.1"},"reference-count":33,"publisher":"BMJ","issue":"9","license":[{"start":{"date-parts":[[2023,8,31]],"date-time":"2023-08-31T00:00:00Z","timestamp":1693440000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Circio Holding ASA","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2023,8,4]]},"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this open-label, randomized study, patients with unresectable MPM received intratumoral ONCOS-102 (3\u00d710\n                      <jats:sup>11<\/jats:sup>\n                      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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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 \u22653 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-na\u00efve 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2023-007552","type":"journal-article","created":{"date-parts":[[2023,9,3]],"date-time":"2023-09-03T20:35:16Z","timestamp":1693773316000},"page":"e007552","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":41,"title":["ONCOS-102 plus pemetrexed and platinum chemotherapy in malignant pleural mesothelioma: a randomized phase 2 study investigating clinical outcomes and the tumor microenvironment"],"prefix":"10.1136","volume":"11","author":[{"given":"Santiago","family":"Ponce","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Hospital Universitario 12 de Octubre, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susana","family":"Cedr\u00e9s","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Vall d'Hebron University Hospital, Barcelona, Spain"},{"name":"Vall d'Hebron Institute of Oncology, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Ricordel","sequence":"additional","affiliation":[{"name":"Department of Pulmonology, Centre Hospitalier Universitaire de Rennes, Rennes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Isambert","sequence":"additional","affiliation":[{"name":"Centre Georges-Fran\u00e7ois Leclerc, Dijon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santiago","family":"Viteri","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Instituto Oncol\u00f3gico Rosell, Grupo Quironsalud, Hospital Universitario Dexeus, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mercedes","family":"Herrera-Juarez","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Hospital Universitario 12 de Octubre, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Martinez-Marti","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Vall d'Hebron University Hospital, Barcelona, Spain"},{"name":"Vall d'Hebron Institute of Oncology, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Navarro","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Vall d'Hebron University Hospital, Barcelona, Spain"},{"name":"Vall d'Hebron Institute of Oncology, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathieu","family":"Lederlin","sequence":"additional","affiliation":[{"name":"Department of Radiology, Centre Hospitalier Universitaire de Rennes, Rennes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Serres","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Vall d'Hebron University Hospital, Barcelona, Spain"},{"name":"Vall d'Hebron Institute of Oncology, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon","family":"Zugazagoitia","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Hospital Universitario 12 de Octubre, Madrid, Spain"},{"name":"H12O-CNIO Lung Cancer Research Unit, Madrid, Spain"},{"name":"Department of Medicine, Complutense University of Madrid, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia","family":"Vetrhus","sequence":"additional","affiliation":[{"name":"Research and Development, Circio Holding ASA, Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magnus","family":"Jaderberg","sequence":"additional","affiliation":[{"name":"Research and Development, Circio Holding ASA, Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7573-9657","authenticated-orcid":false,"given":"Thomas Birkballe","family":"Hansen","sequence":"additional","affiliation":[{"name":"Research and Development, Circio Holding ASA, Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Levitsky","sequence":"additional","affiliation":[{"name":"Research and Development, Circio Holding ASA, Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Paz-Ares","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Hospital Universitario 12 de Octubre, Madrid, Spain"},{"name":"H12O-CNIO Lung Cancer Research Unit, Madrid, 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