The self-adjuvanted RNActive vaccine (CV9103) appears to be well-tolerated and immunogenic in men with advanced castration-resistant prostate cancer, according to a new phase I/IIa study. German researchers have been studying this new vaccine approach and they believe it has the potential to improve outcomes in men with resistant disease.
CV9103 is a sequence-optimized, chemically unmodified mRNA immunotherapy targeting four antigens: prostate-specific antigen (PSA), prostate-specific membrane antigen (PSMA), prostate stem cell antigen (PSCA), and six-transmembrane epithelial antigen of the prostate 1 (STEAP1). These antigens are frequently and almost exclusively expressed in the prostate and overexpressed in prostate cancer, according to the researchers. However, they noted that PSMA is also overexpressed in other cancers. These antigens were picked for the vaccine because they are mainly found on residual prostate cancer cells after radical prostatectomy or radiation.
German researchers conducted a study with CV9103 in 44 patients with advanced castration-resistant prostate cancer who were enrolled at 12 centers in Germany and Italy. The primary endpoint of the study was safety and tolerability, and the secondary endpoints included induction of antigen specific immune responses monitored at baseline and at weeks 5, 9, and 17.
A quantitative analysis of Enzyme-Linked Immuno Spot (ELISpot), Intracellular Cytokine Staining (ICS), and tetramer staining assays revealed that CV9103 was able to induce both CD4 and CD8 T-cell responses. Of the 33 evaluable patients treated at 1280 μg, a cellular immune response could be detected in 76% of the patients (n= 25). The researchers, who published their findings in the Journal for ImmunoTherapy of Cancer, found that immune responses against all four antigens could be induced, indicating the versatility of the platform.
The study demonstrated that CV9103 was well-tolerated and the majority of treatment-related adverse events were mild to moderate. The most frequent treatment-related side effects were injection site erythema (61%) and injection site reaction (48%). The investigators also noted that there may have been possible treatment-related urinary retention, which occurred in three of the 33 patients.
"The data generated by this phase I/IIa clinical study demonstrate that CV9103 mRNA was well-tolerated and immunogenic. Furthermore, a trend towards longer survival time was also observed in immune responders,” said senior author of the paper Arnulf Stenzl, MD, who is the Medical Director of the Department of Urology, University of Tübingen Medical School, Tübingen, Germany. “Based on these results, it is evident that this mRNA technology warrants further clinical investigation.”
The researchers are now conducting a randomized, placebo-controlled, phase IIb study in 197 prostate cancer patients with the next generation experimental vaccine CV9104. This second vaccine (CV9104) targets six antigens, including the additional antigens prostatic acid phosphatase (PAP) and MUC1.
- Kubler H, Scheel B, Gnad-Vogt U, et al. (2015). Self-adjuvanted mRNA vaccination in advanced prostate cancer patients: a first-in-man phase I/IIa study. Journal for ImmunoTherapy of Cancer.
- PRNewswire. (2015). CureVac Announces Phase I/IIa Clinical Study Data of its mRNA Cancer Immunotherapy in Prostate Cancer Published in the Journal for ImmunoTherapy of Cancer.