Local activation of innate immune signaling pathways, such as Toll-like Receptors (TLRs) or RIG-I-like Receptors (RLRs), is a promising cancer immunotherapeutic approach to overcome the tumor immunosuppressive microenvironment and to induce/restore anti-tumor immunity. CV8102 consists of a single-stranded, non-coding RNA complexed with a cationic peptide and acts as an agonist to human TLR-7, -8 and RLRs. Local administration of CV8102 was shown to induce upregulation of inflammatory cytokines, chemokines and IFN-y related genes at the injection site followed by activation of T, NK, NKT cells and migratory dendritic cells in the draining lymph node (Heidenreich 2015; Ziegler 2017). In a syngeneic murine model, intratumoral (IT) delivery of CV8102 induced dose-dependent anti-tumor activity and synergized with systemic anti-PD1 antibody treatment.
This phase I study is evaluating IT injection of CV8102 alone or in combination with a systemic anti-PD-1 antibody in patients with advanced solid tumors. Patients with advanced inoperable melanoma, cutaneous/head and neck squamous cell or adenoid cystic carcinoma and at least one lesion accessible for IT injection are eligible. After determination of the maximum tolerated/ recommended dose of CV8102 alone and in combination with an anti-PD1 antibody, expansion cohorts are planned in different indications. A Bayesian logistic regression model with overdose control will be used to guide the dose escalation. Patients in each cohort will receive up to 8 injections into a single tumor lesion over a 12 weeks period. The primary objective is to determine safety and tolerability, secondary/explorative objectives are to evaluate tumor response and changes in tumor tissue and blood-based biomarkers. The study has been initiated and enrollment is ongoing.
Clinical trial identification
Legal entity responsible for the study
CureVac AG, Paul-Ehrlich-Str. 15, 72076 Tübingen, Germany.
Has not received any funding.
P. Terheyden: Honoraria, Travel expenses: Novartis, Merck, Roche, BMS, Biofrontera; Advisory board: Roche, BMS, Sanofi Novartis, Merck. L. Heinzerling: Consultant: CureVac AG PI in clinical study at site Erlangen. P. Mohr: Consultant or advisory role: Merck, Roche, GSK, BMS, Novartis, SciBase, LEO; Honoraria: GSK, Roche, Merck, BMS, Novartis, LEO, SciBase; Research funding: Merck. F. Kiecker: Payments, Travel grants for symposia, Advisory boards, Meetings: Amgen, BMS, Merck-Serono, MSD, Novartis, Pierre-Fabre, Regeneron, Roche. J.C. Becker: Speaker honoraria: Amgen, MerckSerono and Pfizer; Advisory board honoraria: Amgen, CureVac, eTheRNA, Lytix, MerckSerono, Novartis, Rigontec, Takeda; Research funding: Boehringer Ingelheim, BMS, MerckSerono. U. Gnad-Vogt: Stock, Other ownership interests: Bristol-Myers Squibb. All other authors have declared no conflicts of interest.