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15.02.2019 | Clinical Trial Report

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

verfasst von: 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

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 5/2019

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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⁺CD38^hi 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.

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Titel: A phase I/IIa study of the mRNA-based cancer immunotherapy CV9201 in patients with stage IIIB/IV non-small cell lung cancer
verfasst von: 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
Publikationsdatum: 15.02.2019
Verlag: Springer Berlin Heidelberg
Erschienen in: Cancer Immunology, Immunotherapy / Ausgabe 5/2019
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-019-02315-x

Springer Medizin

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

Abstract

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Springer Medizin

Abstract

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