A phase I/IIa study of the mRNA-based cancer immunotherapy CV9201 in patients with stage IIIB/IV non-small cell lung cancer

  • Martin Sebastian
  • Andreas Schröder
  • Birgit Scheel
  • Henoch S Hong
  • Anke Muth
  • Lotta von Boehmer
  • Alfred Zippelius
  • Frank Mayer
  • Martin Reck
  • Djordje Atanackovic
  • Michael Thomas
  • Folker Schneller
  • Jan Stöhlmacher
  • Helga Bernhard
  • Andreas Gröschel
  • Thomas Lander
  • Jochen Probst
  • Tanja Strack
  • Volker Wiegand
  • Ulrike Gnad-Vogt
  • Karl-Josef Kallen
  • Ingmar Hoerr
  • Florian von der Muelbe
  • Mariola Fotin-Mleczek
  • Alexander Knuth
  • Sven D Koch

Beteiligte Einrichtungen

Abstract

CV9201 is an RNActive®-based cancer immunotherapy encoding five non-small cell lung cancer-antigens: New York esophageal squamous cell carcinoma-1, melanoma antigen family C1/C2, survivin, and trophoblast glycoprotein. In a phase I/IIa dose-escalation trial, 46 patients with locally advanced (n = 7) or metastatic (n = 39) NSCLC and at least stable disease after first-line treatment received five intradermal CV9201 injections (400-1600 µg of mRNA). The primary objective of the trial was to assess safety. Secondary objectives included assessment of antibody and ex vivo T cell responses against the five antigens, and changes in immune cell populations. All CV9201 dose levels were well-tolerated and the recommended dose for phase IIa was 1600 µg. Most AEs were mild-to-moderate injection site reactions and flu-like symptoms. Three (7%) patients had grade 3 related AEs. No related grade 4/5 or related serious AEs occurred. In phase IIa, antigen-specific immune responses against ≥ 1 antigen were detected in 63% of evaluable patients after treatment. The frequency of activated IgD+CD38hi B cells increased > twofold in 18/30 (60%) evaluable patients. 9/29 (31%) evaluable patients in phase IIa had stable disease and 20/29 (69%) had progressive disease. Median progression-free and overall survival were 5.0 months (95% CI 1.8-6.3) and 10.8 months (8.1-16.7) from first administration, respectively. Two- and 3-year survival rates were 26.7% and 20.7%, respectively. CV9201 was well-tolerated and immune responses could be detected after treatment supporting further clinical investigation.

Bibliografische Daten

OriginalspracheEnglisch
ISSN0340-7004
DOIs
StatusVeröffentlicht - 05.2019
PubMed 30770959