title: Phase Ib study evaluating a self-adjuvanted mRNA cancer vaccine (RNActive®) combined with local radiation as consolidation and maintenance treatment for patients with stage IV non-small cell lung cancer.
abstract: BACKGROUND
  Advanced non-small cell lung cancer (NSCLC) represents a significant unmet medical need. Despite advances with targeted therapies in a small subset of patients, fewer than 20% of patients survive for more than two years after diagnosis. Cancer vaccines are a promising therapeutic approach that offers the potential for durable responses through the engagement of the patient's own immune system. CV9202 is a self-adjuvanting mRNA vaccine that targets six antigens commonly expressed in NSCLC (NY-ESO-1, MAGEC1, MAGEC2, 5 T4, survivin, and MUC1).
  
  
  METHODS
  The trial will assess the safety and tolerability of CV9202 vaccination combined with local radiation designed to enhance immune responses and will include patients with stage IV NSCLC and a response or stable disease after first-line chemotherapy or therapy with an EGFR tyrosine kinase inhibitor. Three histological and molecular subtypes of NSCLC will be investigated (squamous and non-squamous cell with/without EGFR mutations). All patients will receive two initial vaccinations with CV9202 prior to local radiotherapy (5 GY per day for four successive days) followed by further vaccinations until disease progression. The primary endpoint of the study is the number of patients experiencing Grade >3 treatment-related adverse events. Pharmacodynamic analyses include the assessment of immune responses to the antigens encoded by CV9202 and others not included in the panel (antigen spreading) and standard efficacy assessments.
  
  
  CONCLUSIONS
  RNActive self-adjuvanted mRNA vaccines offer the potential for simultaneously inducing immune responses to a wide panel of antigens commonly expressed in tumors. This trial will assess the feasibility of this approach in combination with local radiotherapy in NSCLC patients.
  
  
  BACKGROUND
  Clinicaltrials.gov: NCT01915524/EudraCT No.: 2012-004230-41.
authors.forename: Martin
authors.initials: M
authors.lastname: Sebastian
authors.forename: Alexandros
authors.initials: A
authors.lastname: Papachristofilou
authors.forename: Christian
authors.initials: C
authors.lastname: Weiss
authors.forename: Martin
authors.initials: M
authors.lastname: Früh
authors.forename: Richard
authors.initials: R
authors.lastname: Cathomas
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hilbe
authors.forename: Thomas
authors.initials: T
authors.lastname: Wehler
authors.forename: Gerd
authors.initials: G
authors.lastname: Rippin
authors.forename: Sven D
authors.initials: SD
authors.lastname: Koch
authors.forename: Birgit
authors.initials: B
authors.lastname: Scheel
authors.forename: Mariola
authors.initials: M
authors.lastname: Fotin-Mleczek
authors.forename: Regina
authors.initials: R
authors.lastname: Heidenreich
authors.forename: Karl-Josef
authors.initials: KJ
authors.lastname: Kallen
authors.forename: Ulrike
authors.initials: U
authors.lastname: Gnad-Vogt
authors.affiliation: Department of Oncology, University Hospital Basel, Petersgraben 4, CH - 4031 Basel, Switzerland. Alfred.Zippelius@usb.ch.
authors.forename: Alfred
authors.initials: A
authors.lastname: Zippelius
mesh_terms: D019496:Cancer Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics* / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D006801:Humans; D008175:Lung Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D012333:RNA, Messenger / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D011829:Radiation Dosage; D011878:Radiotherapy; D016896:Treatment Outcome
chemical_list: D019496:Cancer Vaccines; D012333:RNA, Messenger