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
Background 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-naïve or anti-PD-1 therapy-refractory cut...
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BMJ Publishing Group
2025-02-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/13/2/e009352.full |
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| author | Lucie Heinzerling Michael Fluck Caroline Robert Celeste Lebbe Erika Richtig Sven D Koch Ulrike Gnad-Vogt Tobias Seibel Thomas Eigentler Juan Martin-Liberal Sebastian Ochsenreither Peter Mohr Patrick Terheyden Carsten Weishaupt Michael Erdmann Lukas Koch Ainara Soria Igor Samoylenko Jürgen Krauß Peter Brossart Franz Georg Bauernfeind Marina Gonzalez Peter Wengenmayer Ioannis Thomas Artem Poltoratskiy Marina Sekacheva Beate Schmitt-Bormann Gianluca Quintini Martin Falk Paula Codó Arjun Oberoi Jana Hess Yulia Semiletova Casilda Llacer Perez Oliver Schönborn-Kellenberger |
| author_facet | Lucie Heinzerling Michael Fluck Caroline Robert Celeste Lebbe Erika Richtig Sven D Koch Ulrike Gnad-Vogt Tobias Seibel Thomas Eigentler Juan Martin-Liberal Sebastian Ochsenreither Peter Mohr Patrick Terheyden Carsten Weishaupt Michael Erdmann Lukas Koch Ainara Soria Igor Samoylenko Jürgen Krauß Peter Brossart Franz Georg Bauernfeind Marina Gonzalez Peter Wengenmayer Ioannis Thomas Artem Poltoratskiy Marina Sekacheva Beate Schmitt-Bormann Gianluca Quintini Martin Falk Paula Codó Arjun Oberoi Jana Hess Yulia Semiletova Casilda Llacer Perez Oliver Schönborn-Kellenberger |
| author_sort | Lucie Heinzerling |
| collection | DOAJ |
| description | Background 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-naïve 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.Methods 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.Results 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 µg 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 µg. 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.Conclusions IT CV8102 was generally well tolerated with preliminary signs of efficacy as monotherapy and in combination with a PD-1 inhibitor.Trial registration number NCT03291002. |
| format | Article |
| id | doaj-art-fef23ac8038746b09f1f1adc72f9e55e |
| institution | Kabale University |
| issn | 2051-1426 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-fef23ac8038746b09f1f1adc72f9e55e2025-02-05T04:40:11ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262025-02-0113210.1136/jitc-2024-009352Phase 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 carcinomaLucie Heinzerling0Michael Fluck1Caroline Robert2Celeste Lebbe3Erika Richtig4Sven D Koch5Ulrike Gnad-Vogt6Tobias Seibel7Thomas Eigentler8Juan Martin-Liberal9Sebastian Ochsenreither10Peter Mohr11Patrick Terheyden12Carsten Weishaupt13Michael Erdmann14Lukas Koch15Ainara Soria16Igor Samoylenko17Jürgen Krauß18Peter Brossart19Franz Georg Bauernfeind20Marina Gonzalez21Peter Wengenmayer22Ioannis Thomas23Artem Poltoratskiy24Marina Sekacheva25Beate Schmitt-Bormann26Gianluca Quintini27Martin Falk28Paula Codó29Arjun Oberoi30Jana Hess31Yulia Semiletova32Casilda Llacer Perez33Oliver Schönborn-Kellenberger34University Hospital Erlangen, Erlangen, Bayern, GermanyDepartment of Oncology Hornheide, Fachklinik Hornheide, Münster, GermanyDepartment of Oncology, Institut Gustave Roussy and Université Paris Saclay, Villejuif, FranceUniversité Paris Cite, Dermato-Oncology and CIC AP-HP Hôpital Saint Louis and Cancer Institute APHP, Nord-Université Paris Cite, INSERM U976, Université Paris Cité, Paris, FranceDepartment of Dematology, Medical University of Graz, Graz, AustriaCureVac SE, Tübingen, GermanyCureVac SE, Wiesbaden, GermanyCureVac SE, Tübingen, GermanyDepartment of Dermatology, Venereology and Allergology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, Berlin, Berlin, GermanyMedical Oncology Department, Catalan Institute of Oncology (ICO), Catalan Institute of Oncology, 08908 Barcelona, SpainCharité Comprehensive Cancer Center, Charité - Universitätsmedizin Berlin, Berlin, GermanyDepartment of Dermatology, Elbe Hospital, Buxtehude, Niedersachsen, GermanyDepartment of Dermatology, University of Lübeck, Lubeck, Schleswig-Holstein, GermanyDepartment of Dermatology, Skin Cancer Center, University Clinic Münster, Munster, GermanyDepartment of Dermatology, Uniklinikum Erlangen, Comprehensive Cancer Center Erlangen - European Metropolitan Area of Nürnberg (CCC ER-EMN), Friedrich-Alexander-Universität (FAU), Erlangen, GermanyDepartment of Dermatology, Medical University of Graz, Graz, AustriaDepartment of Medical Oncology, Hospital Universitario Ramón y Cajal, Madrid, Madrid, SpainOncodermatology and surgical immunology unit, Blokhin Russian Cancer Research Center, Ministry of Health of Russia, Moscow, Russian FederationNational Center for Tumor Diseases, Heidelberg, GermanyDepartment of Oncology, Hematology. Cell and Immunotherapies, University Hospital Bonn, Bonn, Nordrhein-Westfalen, GermanyDepartment of Oncology, Hematology. Cell and Immunotherapies, University Hospital Bonn, Bonn, Nordrhein-Westfalen, GermanyCureVac SE, Tübingen, GermanyCureVac SE, Tübingen, GermanyFaculty of Medicine, University of Tübingen, Tubingen, GermanyPetrov Research Institute of Oncology, St Petersburg, Russian FederationInstitute for Personalized Oncology of the World-Class Research Center Digital Biodesign and Personalized Healthcare, Schenenov University, Moscow, Russian FederationCureVac SE, Wiesbaden, GermanyCureVac SE, Tübingen, GermanyCureVac SE, Wiesbaden, GermanyCureVac SE, Tübingen, GermanyVall d’Hebron University Hospital and Vall d’Hebron Institute of Oncology, Barcelona, SpainCureVac SE, Tübingen, GermanySt Petersburg State University Hospital, St Petersburg, Russian FederationMedical Oncology Intercenter Unit, Regional and Virgen de la Victoria University Hospitals, IBIMA, Malaga, SpainCureVac SE, Tübingen, GermanyBackground 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-naïve 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.Methods 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.Results 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 µg 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 µg. 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.Conclusions IT CV8102 was generally well tolerated with preliminary signs of efficacy as monotherapy and in combination with a PD-1 inhibitor.Trial registration number NCT03291002.https://jitc.bmj.com/content/13/2/e009352.full |
| spellingShingle | Lucie Heinzerling Michael Fluck Caroline Robert Celeste Lebbe Erika Richtig Sven D Koch Ulrike Gnad-Vogt Tobias Seibel Thomas Eigentler Juan Martin-Liberal Sebastian Ochsenreither Peter Mohr Patrick Terheyden Carsten Weishaupt Michael Erdmann Lukas Koch Ainara Soria Igor Samoylenko Jürgen Krauß Peter Brossart Franz Georg Bauernfeind Marina Gonzalez Peter Wengenmayer Ioannis Thomas Artem Poltoratskiy Marina Sekacheva Beate Schmitt-Bormann Gianluca Quintini Martin Falk Paula Codó Arjun Oberoi Jana Hess Yulia Semiletova Casilda Llacer Perez Oliver Schönborn-Kellenberger 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 Journal for ImmunoTherapy of Cancer |
| 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| url | https://jitc.bmj.com/content/13/2/e009352.full |
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