A phase I/IIa study of the mRNA-based cancer immunotherapy CV9201 in patients with stage IIIB/IV non-small cell lung cancer
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A phase I/IIa study of the mRNA-based cancer immunotherapy CV9201 in patients with stage IIIB/IV non-small cell lung cancer. / Sebastian, Martin; Schröder, Andreas; Scheel, Birgit; Hong, Henoch S; Muth, Anke; von Boehmer, Lotta; Zippelius, Alfred; Mayer, Frank; Reck, Martin; Atanackovic, Djordje; Thomas, Michael; Schneller, Folker; Stöhlmacher, Jan; Bernhard, Helga; Gröschel, Andreas; Lander, Thomas; Probst, Jochen; Strack, Tanja; Wiegand, Volker; Gnad-Vogt, Ulrike; Kallen, Karl-Josef; Hoerr, Ingmar; von der Muelbe, Florian; Fotin-Mleczek, Mariola; Knuth, Alexander; Koch, Sven D.
in: CANCER IMMUNOL IMMUN, Jahrgang 68, Nr. 5, 05.2019, S. 799-812.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - A phase I/IIa study of the mRNA-based cancer immunotherapy CV9201 in patients with stage IIIB/IV non-small cell lung cancer
AU - Sebastian, Martin
AU - Schröder, Andreas
AU - Scheel, Birgit
AU - Hong, Henoch S
AU - Muth, Anke
AU - von Boehmer, Lotta
AU - Zippelius, Alfred
AU - Mayer, Frank
AU - Reck, Martin
AU - Atanackovic, Djordje
AU - Thomas, Michael
AU - Schneller, Folker
AU - Stöhlmacher, Jan
AU - Bernhard, Helga
AU - Gröschel, Andreas
AU - Lander, Thomas
AU - Probst, Jochen
AU - Strack, Tanja
AU - Wiegand, Volker
AU - Gnad-Vogt, Ulrike
AU - Kallen, Karl-Josef
AU - Hoerr, Ingmar
AU - von der Muelbe, Florian
AU - Fotin-Mleczek, Mariola
AU - Knuth, Alexander
AU - Koch, Sven D
PY - 2019/5
Y1 - 2019/5
N2 - 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.
AB - 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.
KW - Aged
KW - Aged, 80 and over
KW - Antigens, Neoplasm/genetics
KW - B-Lymphocytes/immunology
KW - Cancer Vaccines/genetics
KW - Carcinoma, Non-Small-Cell Lung/immunology
KW - Cells, Cultured
KW - Female
KW - Humans
KW - Immunotherapy/adverse effects
KW - Injection Site Reaction/etiology
KW - Lung Neoplasms/immunology
KW - Lymphocyte Activation
KW - Male
KW - Middle Aged
KW - Neoplasm Staging
KW - RNA, Messenger/administration & dosage
KW - Survival Analysis
KW - T-Lymphocytes/immunology
U2 - 10.1007/s00262-019-02315-x
DO - 10.1007/s00262-019-02315-x
M3 - SCORING: Journal article
C2 - 30770959
VL - 68
SP - 799
EP - 812
JO - CANCER IMMUNOL IMMUN
JF - CANCER IMMUNOL IMMUN
SN - 0340-7004
IS - 5
ER -