title: Self-adjuvanted mRNA vaccination in advanced prostate cancer patients: a first-in-man phase I/IIa study.
abstract: BACKGROUND
  CV9103 is a prostate-cancer vaccine containing self-adjuvanted mRNA (RNActive®) encoding the antigens PSA, PSCA, PSMA, and STEAP1. This phase I/IIa study evaluated safety and immunogenicity of CV9103 in patients with advanced castration-resistant prostate-cancer.
  
  
  METHODS
  44 Patients received up to 5 intra-dermal vaccinations. Three dose levels of total mRNA were tested in Phase I in cohorts of 3-6 patients to determine a recommended dose. In phase II, 32 additional patients were treated at the recommended dose. The primary endpoint was safety and tolerability, the secondary endpoint was induction of antigen specific immune responses monitored at baseline and at weeks 5, 9 and 17.
  
  
  RESULTS
  The most frequent adverse events were grade 1/2 injection site erythema, injection site reactions, fatigue, pyrexia, chills and influenza-like illness. Possibly treatment related urinary retention occurred in 3 patients. The recommended dose was 1280 μg. A total of 26/33 evaluable patients treated at 1280 μg developed an immune response, directed against multiple antigens in 15 out of 33 patients. One patient showed a confirmed PSA response. In the subgroup of 36 metastatic patients, the Kaplan-Meier estimate of median overall survival was 31.4 months [95 % CI: 21.2; n.a].
  
  
  CONCLUSIONS
  The self-adjuvanted RNActive® vaccine CV9103 was well tolerated and immunogenic. The technology is a versatile, fast and cost-effective platform allowing for creation of vaccines. The follow-up vaccine CV9104 including the additional antigens prostatic acid phosphatase (PAP) and Muc1 is currently being tested in a randomized phase IIb trial to assess the clinical benefit induced by this new vaccination approach.
  
  
  BACKGROUND
  EU Clinical Trials Register: EudraCT number 2008-003967-37, registered 27 Jan 2009.
authors.affiliation: Klinikum rechts der Isar der Technischen Universität München, Munich, Germany.
authors.forename: Hubert
authors.initials: H
authors.lastname: Kübler
authors.affiliation: CureVac GmbH, Paul-Ehrlich-Str. 15, Tuebingen, 72076 Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Scheel
authors.affiliation: CureVac GmbH, Paul-Ehrlich-Str. 15, Tuebingen, 72076 Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Gnad-Vogt
authors.affiliation: Charité University Hospital Berlin, Berlin, Germany.
authors.forename: Kurt
authors.initials: K
authors.lastname: Miller
authors.affiliation: University Hospital Freiburg, Freiburg, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schultze-Seemann
authors.affiliation: Universitäty Hospital Essen, Essen, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Vom Dorp
authors.affiliation: San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Parmiani
authors.affiliation: University Hospital of the Johannes-Gutenberg-University Mainz, Mainz, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Hampel
authors.affiliation: Ortenau Klinikum Offenburg-Gengenbach, Offenburg, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Wedel
authors.affiliation: University Hospital Göttingen, Göttingen/University Hospital Mannheim, Mannheim, Germany.
authors.forename: Lutz
authors.initials: L
authors.lastname: Trojan
authors.affiliation: University Hospital Schleswig-Holstein Campus Luebeck, Luebeck, Germany.
authors.forename: Dieter
authors.initials: D
authors.lastname: Jocham
authors.affiliation: Klinikum rechts der Isar der Technischen Universität München, Munich, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Maurer
authors.affiliation: Rippin-Consulting, Solingen, Germany.
authors.forename: Gerd
authors.initials: G
authors.lastname: Rippin
authors.affiliation: CureVac GmbH, Paul-Ehrlich-Str. 15, Tuebingen, 72076 Germany.
authors.forename: Mariola
authors.initials: M
authors.lastname: Fotin-Mleczek
authors.affiliation: CureVac GmbH, Paul-Ehrlich-Str. 15, Tuebingen, 72076 Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: von der Mülbe
authors.affiliation: CureVac GmbH, Paul-Ehrlich-Str. 15, Tuebingen, 72076 Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Probst
authors.affiliation: CureVac GmbH, Paul-Ehrlich-Str. 15, Tuebingen, 72076 Germany.
authors.forename: Ingmar
authors.initials: I
authors.lastname: Hoerr
authors.affiliation: CureVac GmbH, Paul-Ehrlich-Str. 15, Tuebingen, 72076 Germany.
authors.forename: Karl-Josef
authors.initials: KJ
authors.lastname: Kallen
authors.affiliation: CureVac GmbH, Paul-Ehrlich-Str. 15, Tuebingen, 72076 Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Lander
authors.affiliation: University Hospital Tuebingen, Tuebingen, Germany.
authors.forename: Arnulf
authors.initials: A
authors.lastname: Stenzl