Sistema de Salut de Catalunya
Institut Català de la Salut
[Eigentler T] Department of Dermatology, Venereology and Allergology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, Berlin, Berlin, Germany. [Thomas I] Faculty of Medicine, University of Tübingen, Tubingen, Germany. [Samoylenko I] Oncodermatology and surgical immunology unit, Blokhin Russian Cancer Research Center, Ministry of Health of Russia, Moscow, Russian Federation. [Erdmann M] Department of Dermatology, Uniklinikum Erlangen, Comprehensive Cancer Center Erlangen - European Metropolitan Area of Nürnberg (CCC ER-EMN), FriedrichAlexander-Universität (FAU), Erlangen, Germany. [Heinzerling L] Department of Dermatology & Allergy, LMU University Hospital, LMU Munich, München, Germany. University Hospital Erlangen, Erlangen, Bayern, Germany. [Ochsenreither S] 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. [Oberoi A] Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain
Vall d'Hebron Barcelona Hospital Campus
2025-04-09T08:58:14Z
2025-04-09T08:58:14Z
2025-02
Head and neck cancer; Immunotherapy; Skin cancer
Càncer de cap i coll; Immunoteràpia; Càncer de pell
Cáncer de cabeza y cuello; Inmunoterapia; Cáncer de piel
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.
This study was funded by CureVac SE.
Article
Published version
English
Pell - Càncer - Tractament; Cap - Càncer - Tractament; Coll - Càncer - Tractament; Avaluació de resultats (Assistència sanitària); Quimioteràpia combinada; DISEASES::Neoplasms::Neoplasms::Neoplasms by Site::Head and Neck Neoplasms::Squamous Cell Carcinoma of Head and Neck; Other subheadings::Other subheadings::Other subheadings::/drug therapy; DISEASES::Neoplasms::Neoplasms by Site::Skin Neoplasms; Other subheadings::Other subheadings::Other subheadings::/drug therapy; ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Investigative Techniques::Toxicity Tests::Maximum Tolerated Dose; ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols; ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Diagnosis::Prognosis::Treatment Outcome; ENFERMEDADES::neoplasias::neoplasias::neoplasias por localización::neoplasias de cabeza y cuello::carcinoma de células escamosas de cabeza y cuello; Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia; ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias cutáneas; Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia; TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::técnicas de investigación::pruebas de toxicidad::dosis máxima tolerada; TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada; TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::diagnóstico::pronóstico::resultado del tratamiento
BMJ
Journal for ImmunoTherapy of Cancer;13(2)
https://doi.org/10.1136/jitc-2024-009352
Attribution-NonCommercial 4.0 International
http://creativecommons.org/licenses/by-nc/4.0/
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