A Phase I Dose-Escalation And Expansion Study Of Intratumoral Cv8102 As Single-Agent Or In Combination With Anti-Pd-1 Antibodies In Patients With Advanced Solid Tumors.

3096 Background: CV8102 is a non-coding, non-capped RNA that activates the innate (via TLR7/8, RIG-I) and adaptive immunity dose-dependently. CV8102 injected intratumorally (i.t.), as a single agent or combined with systemic anti-PD-1 antibody (Ab) led to tumor growth inhibition in animal models and showed synergism with PD-1 blockade. 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. [NCT03291002]. Results: As of December 2019, 23 patients in the cohort A (single agent) and 13 patients in cohort C (combination with anti-PD-1 Ab) were exposed to at least one dose of CV8102 at dose levels of 25-600 µg (single agent) and 25-450 µg (combination). No dose limiting toxicities (DLTs) were observed within the first two weeks of study drug treatment. Most frequent TEAEs were G1/2 fatigue, fever, chills and headache. 4 (17%) patients (pts) in cohort A and 3 (23%) pts in cohort C experienced related G3 TEAEs that were manageable with supportive treatment (liver enzyme increases (3), abscess at injection site (1), hypertension (1), asymptomatic elevation of pancreatic enzymes (2)). In cohort A, 2 cMEL patients experienced an objective response according to RECIST 1.1 (1 CR in a PD-1 naïve pt and 1 PR in a PD-1 refractory pt) and 2 further pts (cMEL, hnSCC) showed SD with shrinkage of tumor lesions. Conclusions: CV8102 i.t. was well tolerated without dose limiting toxicities to date and showed evidence of single agent activity. Updated results on safety, efficacy and serum biomarkers will be presented. Clinical trial information: NCT03291002 .