CV9104 is a multivalent mRNA-based active cancer immunotherapy containing sequence-optimized free and protamine complexed mRNA coding for six prostate cancer associated antigens (PSA, PSMA, PSCA, STEAP1, PAP and MUC1). CV9104 has been investigated in a placebo controlled Phase IIb study in pts with metastatic castrate-resistant PC. Administration of mRNA based immunotherapy by needle free jet devices has been shown to improve antigen expression and immunogenicity vs needle injection in preclinical models. The purpose of this study was to evaluate immune responses and safety of CV9104 administered by conventional intradermal (cID) injection or with a needle-free ID (nfID) injection device in pts with intermediate/high-risk localized PC.
48 pts with intermediate or high risk localized PC and an indication to undergo RPE were randomized in a 1:1:1 ratio to receive presurgical CV9104 by nfID injection (960 µg mRNA per administration) (A), or cID injection (1920 µg mRNA per administration) (B), or no treatment (C). CV9104 was administered in weeks 1, 2, 3 and 5 before RPE was performed in week 6-7. Postoperative CV9104 was offered to all pts with high-risk PC. Cellular (against all antigens) and humoral immune responders (against PSA, STEAP1, PAP, MUC1) were determined in blood at week 6-7 before RPE and 8 weeks after surgery. Further samples (prostatectomy, exprimate urine, serum) were collected for exploratory biomarker analyses.
48 pts were randomized (A: 15; B: 17; C: 16); Treatment with CV9104 was well tolerated using either nflD or clD injection. Most frequent adverse events (AEs) in Arms A and B were Grade 1-2 injection side reactions, transient flu-like symptoms (FLS) and AEs related to RPE. There were no CV9104 related Grade ≥3 AEs or SAEs. FLS were most frequent in Arm B (76.5%) vs Arm A (37.5%) and Arm C (6.3%).
CV9104 was well tolerated using either nflD or clD injection, with a safety profile similar to other previous mRNA-based cancer immunotherapies. Cellular and humoral immune responses including responses per antigen and additional biomarker results will be presented.
Clinical trial identification
EudraCT Number: 2013-004489-32
Legal entity responsible for the study
Sponsor Clinical Trial: CureVac AG
M. Hipp, F. Doener, S.D. Koch, T. Seibel: CureVac employee. U. Klinkhardt, H.S. Hong, S. Brutlach, M. Fotin-Mleczek, U. Gnad-Vogt: CureVac employee. M. Scholl: previous CureVac employee. A. Schroeder: Previous CureVac employee; current employee Merck KGaA. O. Schönborn-Kellenberger: CureVac Consultant. All other authors have declared no conflicts of interest.