{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T01:57:57Z","timestamp":1790387877837,"version":"4.1.0"},"reference-count":28,"publisher":"BMJ","issue":"2","license":[{"start":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T00:00:00Z","timestamp":1738627200000},"content-version":"unspecified","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"CureVac","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":[[2024,11,24]]},"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>CV8102, a toll-like receptor 7\/8 and RIG I agonist, has demonstrated antitumor immune responses in preclinical studies. We investigated intratumoral (IT) administration of CV8102 in patients with anti-programmed cell death protein-1 (PD-1) therapy-na\u00efve or anti-PD-1 therapy-refractory cutaneous melanoma (cMEL) and in patients with advanced cutaneous squamous cell carcinoma, head and neck squamous cell carcinoma and adenoid cystic carcinoma.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>This open-label, cohort-based, phase I dose escalation study aimed to establish the maximum tolerated dose (MTD), recommended dose (RD), safety and preliminary efficacy of CV8102 as monotherapy or in combination with a PD-1 inhibitor. The preliminary efficacy of the RD was assessed in patients with cMEL in the expansion cohorts.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Between September 2017 and October 2022, 98 patients were enrolled in monotherapy and combination therapy dose escalation and dose expansion cohorts. Two patients in the CV8102 monotherapy dose escalation cohort experienced relevant toxicities at the 900\u2009\u00b5g dose level. One patient had Grade 3 aspartate transaminase\/alanine aminotransferase elevation which met dose-limiting toxicity (DLT) criteria. Another patient experienced Grade 3 immune-mediated pneumonitis. No DLTs occurred in the combination therapy dose escalation cohort. The MTD was not formally reached and the RD for expansion was 600\u2009\u00b5g. Common treatment-emergent adverse events were fever (57%), chills (37%) and fatigue (25%). In the dose escalation part, objective responses occurred in 3\/33 patients treated with CV8102 as monotherapy and in 2\/25 patients treated with CV8102 plus a PD-1 inhibitor. In the expansion cohorts in patients with anti-PD-1 therapy-refractory melanoma, 0\/10 patients treated with CV8102 as monotherapy and 5\/30 patients (17%) treated in combination with a PD-1 inhibitor experienced objective responses.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>IT CV8102 was generally well tolerated with preliminary signs of efficacy as monotherapy and in combination with a PD-1 inhibitor.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Trial registration number<\/jats:title>\n                  <jats:p>\n                     <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT03291002\">NCT03291002<\/jats:ext-link>.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jitc-2024-009352","type":"journal-article","created":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T12:50:26Z","timestamp":1738673426000},"page":"e009352","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":10,"title":["Phase I study of intratumoral administration of CV8102 in patients with advanced melanoma, squamous cell carcinoma of the skin, squamous cell carcinoma of the head and neck, or adenoid cystic carcinoma"],"prefix":"10.1136","volume":"13","clinical-trial-number":[{"clinical-trial-number":"nct03291002","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0019-2770","authenticated-orcid":false,"given":"Thomas","family":"Eigentler","sequence":"first","affiliation":[{"name":"Department of Dermatology, Venereology and Allergology, Charit\u00e9 - Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt Universit\u00e4t zu Berlin, Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioannis","family":"Thomas","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of T\u00fcbingen, Tubingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor","family":"Samoylenko","sequence":"additional","affiliation":[{"name":"Oncodermatology and surgical immunology unit, Blokhin Russian Cancer Research Center, Ministry of Health of Russia, Moscow, Russian Federation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Erdmann","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Uniklinikum Erlangen, Comprehensive Cancer Center Erlangen - European Metropolitan Area of N\u00fcrnberg (CCC ER-EMN), Friedrich-Alexander-Universit\u00e4t (FAU), Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9074-8017","authenticated-orcid":false,"given":"Lucie","family":"Heinzerling","sequence":"additional","affiliation":[{"name":"Department of Dermatology & Allergy, LMU University Hospital, LMU Munich, M\u00fcnchen, Germany"},{"name":"University Hospital Erlangen, Erlangen, Bayern, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Ochsenreither","sequence":"additional","affiliation":[{"name":"Charit\u00e9 Comprehensive Cancer Center, Charit\u00e9 - Universit\u00e4tsmedizin Berlin, Berlin, Germany"},{"name":"Department of Hematology, Oncology and Tumor Immunology, Charit\u00e9 - Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt Universit\u00e4t zu Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen","family":"Krauss","sequence":"additional","affiliation":[{"name":"National Center for Tumor Diseases, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arjun","family":"Oberoi","sequence":"additional","affiliation":[{"name":"Vall d\u2019Hebron University Hospital and Vall d\u2019Hebron Institute of Oncology, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Robert","sequence":"additional","affiliation":[{"name":"Department of Oncology, Institut Gustave Roussy and Universit\u00e9 Paris Saclay, Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celeste","family":"Lebbe","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cite, Dermato-Oncology and CIC AP-HP H\u00f4pital Saint Louis and Cancer Institute APHP, Nord-Universit\u00e9 Paris Cite, INSERM U976, Universit\u00e9 Paris Cit\u00e9, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Martin-Liberal","sequence":"additional","affiliation":[{"name":"Medical Oncology Department, Catalan Institute of Oncology (ICO), Catalan Institute of Oncology, 08908 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukas","family":"Koch","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Medical University of Graz, Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika","family":"Richtig","sequence":"additional","affiliation":[{"name":"Department of Dematology, Medical University of Graz, Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5894-1677","authenticated-orcid":false,"given":"Patrick","family":"Terheyden","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of L\u00fcbeck, Lubeck, Schleswig-Holstein, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten","family":"Weishaupt","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Skin Cancer Center, University Clinic M\u00fcnster, Munster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Mohr","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Elbe Hospital, Buxtehude, Niedersachsen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulia","family":"Semiletova","sequence":"additional","affiliation":[{"name":"St Petersburg State University Hospital, St Petersburg, Russian Federation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Casilda Llacer","family":"Perez","sequence":"additional","affiliation":[{"name":"Medical Oncology Intercenter Unit, Regional and Virgen de la Victoria University Hospitals, IBIMA, Malaga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Brossart","sequence":"additional","affiliation":[{"name":"Department of Oncology, Hematology. 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