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Cancer Immunol Immunother. 2019 Feb 15. doi: 10.1007/s00262-019-02315-x. [Epub ahead of print]

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

Author information

1
University Medical Center of the Johannes Gutenberg-University, Mainz, Germany. martin.sebastian@kgu.de.
2
Medizinische Klinik II, Hämatologie/Onkologie, Rheumatologie, Infektiologie, HIV Klinikum der J.W. Goethe-Universität Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt am Main, Germany. martin.sebastian@kgu.de.
3
CureVac AG, Tübingen, Germany.
4
Merck KGaA, Darmstadt, Germany.
5
Klinik für Onkologie, UniversitätsSpital Zürich, Zurich, Switzerland.
6
Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, USA.
7
Klinik für Onkologie, Universitätsspital Basel, Basel, Switzerland.
8
Universitätsklinikum Tübingen, Tübingen, Germany.
9
Praxis und Tagesklinik, Friedrichshafen, Germany.
10
LungenClinic Grosshansdorf, Airway Research Center North (ARCN), German Center for Lung Research (DZL), Grosshansdorf, Germany.
11
Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.
12
Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
13
Internistische Onkologie der Thoraxtumoren, Thoraxklinik im Universitätsklinikum Heidelberg, Translational Lung Research Center Heidelberg (TLRC-H), Member of the German Center for Lung Research (DZL), Heidelberg, Germany.
14
Klinikum rechts der Isar der TUM, Munich, Germany.
15
Universitätsklinikum Carl Gustav Carus, Dresden, Germany.
16
Tumorgenetik Bonn, Bonn, Germany.
17
Klinikum Darmstadt GmbH, Darmstadt, Germany.
18
Universitätsklinikum Aachen, Aachen, Germany.
19
Clemenshospital, Münster, Germany.
20
Sandoz GmbH, Langkampfen, Austria.
21
Kallen Medical Innovation GmbH, Frechen, Germany.
22
National Center for Cancer Care and Research NCCCR, Hamad Medical Corporation, Doha, Qatar.
23
Sandoz Biopharmaceuticals, Department of Clinical Bioanalytics, Oberhaching, Germany.

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.

KEYWORDS:

Active cancer immunotherapy; CV9201; Clinical trial; Immunomonitoring; Non-small cell lung cancer; mRNA

PMID:
30770959
DOI:
10.1007/s00262-019-02315-x

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