2026-04-17T04:45:41Zhttps://recercat.cat/oai/requestoai:recercat.cat:11351/129222025-05-03T03:20:23Zcom_2072_378070com_2072_378040col_2072_378092
RECERCAT
author
Eigentler, Thomas
author
Thomas, Ioannis
author
Samoylenko, Igor
author
Erdmann, Michael
author
Leonhardt, Anna
author
Ochsenreither, Sebastian
author
Oberoi, Arjun
2025-05-03T03:20:22Z
2025-05-03T03:20:22Z
2025-04-09T08:58:14Z2025-04-09T08:58:14Z2025-02
http://hdl.handle.net/11351/12922
Head and neck cancer; Immunotherapy; Skin cancerCàncer de cap i coll; Immunoteràpia; Càncer de pellCáncer de cabeza y cuello; Inmunoterapia; Cáncer de pielBackground 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.
Attribution-NonCommercial 4.0 International http://creativecommons.org/licenses/by-nc/4.0/ info:eu-repo/semantics/openAccess
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
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
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion