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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
Details
; Thomas, Ioannis 2 ; Samoylenko, Igor 3 ; Erdmann, Michael 4 ; Heinzerling, Lucie 5
; Ochsenreither, Sebastian 6 ; Krauss, Jürgen 7 ; Oberoi, Arjun 8 ; Robert, Caroline 9 ; Lebbe, Celeste 10 ; Martin-Liberal, Juan 11 ; Koch, Lukas 12 ; Richtig, Erika 13 ; Terheyden, Patrick 14
; Weishaupt, Carsten 15 ; Mohr, Peter 16 ; Semiletova, Yulia 17 ; Casilda Llacer Perez 18 ; Brossart, Peter 19 ; Bauernfeind, Franz Georg 19 ; Fluck, Michael 20 ; Poltoratskiy, Artem 21 ; Sekacheva, Marina 22 ; Soria, Ainara 23 ; Schmitt-Bormann, Beate 24 ; Gonzalez, Marina 25 ; Heß, Jana 25
; Wengenmayer, Peter 25 ; Seibel, Tobias 25 ; Koch, Sven D 25 ; Quintini, Gianluca 25 ; Codó, Paula 25 ; Falk, Martin 24 ; Schönborn-Kellenberger, Oliver 26 ; Gnad-Vogt, Ulrike 24 1 Department of Dermatology, Venereology and Allergology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, Berlin, Berlin, Germany
2 Faculty of Medicine, University of Tübingen, Tubingen, Germany
3 Oncodermatology and surgical immunology unit, Blokhin Russian Cancer Research Center, Ministry of Health of Russia, Moscow, Russian Federation
4 Department of Dermatology, Uniklinikum Erlangen, Comprehensive Cancer Center Erlangen - European Metropolitan Area of Nürnberg (CCC ER-EMN), Friedrich-Alexander-Universität (FAU), Erlangen, Germany
5 Department of Dermatology & Allergy, LMU University Hospital, LMU Munich, München, Germany; University Hospital Erlangen, Erlangen, Bayern, Germany
6 Charité Comprehensive Cancer Center, Charité - Universitätsmedizin Berlin, Berlin, Germany; Department of Hematology, Oncology and Tumor Immunology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, Berlin, Germany
7 National Center for Tumor Diseases, Heidelberg, Germany
8 Vall d’Hebron University Hospital and Vall d’Hebron Institute of Oncology, Barcelona, Spain
9 Department of Oncology, Institut Gustave Roussy and Université Paris Saclay, Villejuif, France
10 Université 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, France
11 Medical Oncology Department, Catalan Institute of Oncology (ICO), Catalan Institute of Oncology, 08908 Barcelona, Spain
12 Department of Dermatology, Medical University of Graz, Graz, Austria
13 Department of Dematology, Medical University of Graz, Graz, Austria
14 Department of Dermatology, University of Lübeck, Lubeck, Schleswig-Holstein, Germany
15 Department of Dermatology, Skin Cancer Center, University Clinic Münster, Munster, Germany
16 Department of Dermatology, Elbe Hospital, Buxtehude, Niedersachsen, Germany
17 St Petersburg State University Hospital, St Petersburg, Russian Federation
18 Medical Oncology Intercenter Unit, Regional and Virgen de la Victoria University Hospitals, IBIMA, Malaga, Spain
19 Department of Oncology, Hematology. Cell and Immunotherapies, University Hospital Bonn, Bonn, Nordrhein-Westfalen, Germany
20 Department of Oncology Hornheide, Fachklinik Hornheide, Münster, Germany
21 Petrov Research Institute of Oncology, St Petersburg, Russian Federation
22 Institute for Personalized Oncology of the World-Class Research Center "Digital Biodesign and Personalized Healthcare", Schenenov University, Moscow, Russian Federation
23 Department of Medical Oncology, Hospital Universitario Ramón y Cajal, Madrid, Madrid, Spain
24 CureVac SE, Wiesbaden, Germany
25 CureVac SE, Tübingen, Germany
26 CureVac SE, Tübingen, Germany; Cogitars GmbH, Heidelberg, Germany