800?A phase I dose escalation and expansion study of intratumorally administered CV8102 as a single-agent or in combination with anti-PD-1 antibodies in patients with advanced solid tumors

摘要

Background CV8102 is a non-coding, non-capped RNA complexed with a carrier peptide activating the innate (via TLR7/8, RIG-I) and adaptive immune system. 1 2 An ongoing phase I trial is investigating i.t. CV8102 either as a single agent or in combination with systemic anti-PD-1 antibodies in patients with advanced melanoma (MEL), squamous cell carcinoma of the skin (cSCC) or head and neck (hnSCC) and adenoid cystic carcinoma (ACC). Methods An open-label, cohort-based, dose escalation and expansion study in patients with advanced cutaneous melanoma (cMEL), cutaneous squamous cell carcinoma (cSCC), head and neck squamous cell carcinoma (hnSCC) or adenoid cystic carcinoma (ACC) is ongoing investigating i.t. CV8102 as single agent and in combination with anti-PD-1 antibodies.8 intratumoral injections of CV8102 are being administered initially over a 12 week period, while patients benefiting from the single agent therapy may receive further treatment. In an initial dose escalation part the maximum tolerated dose and recommended phase 2 dose for subsequent cohort expansion will be defined. Results As of September 16, 2020, 29 patients have been treated with CV8102 as a single agent (25-900 μg) and 21 patients have received CV8102 (25-900 μg) in combination with anti-PD-1 antibodies. Most frequent treatment related adverse events were mild to moderate fever, fatigue, chills and headache. One patient treated at the 900 μg single agent experienced a dose limiting toxicity (G3 transaminase increase in the context of G2 cytokine release syndrome).Regression of injected and distant noninjected lesions was observed in several patients in the single agent and the anti-PD-1 combination cohorts. Updated safety and efficacy results will be presented. Conclusions CV8102 showed an acceptable tolerability and preliminary evidence of clinical efficacy as single agent and in combination with anti-PD-1- antibodies. Trial Registration NCT03291002 Ethics Approval The study was approved by the Central Ethics Committees in Tuebingen, Germany under 785/2016AMG1, in France under 19.05.17.64111, in Barcelona, Spain under the EudraCT number. Consent Written informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.