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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

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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, Vol. 68, No. 5, 05.2019, p. 799-812.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Sebastian, M, Schröder, A, Scheel, B, Hong, HS, Muth, A, von Boehmer, L, Zippelius, A, Mayer, F, Reck, M, Atanackovic, D, Thomas, M, Schneller, F, Stöhlmacher, J, Bernhard, H, Gröschel, A, Lander, T, Probst, J, Strack, T, Wiegand, V, Gnad-Vogt, U, Kallen, K-J, Hoerr, I, von der Muelbe, F, Fotin-Mleczek, M, Knuth, A & Koch, SD 2019, 'A phase I/IIa study of the mRNA-based cancer immunotherapy CV9201 in patients with stage IIIB/IV non-small cell lung cancer', CANCER IMMUNOL IMMUN, vol. 68, no. 5, pp. 799-812. https://doi.org/10.1007/s00262-019-02315-x

APA

Sebastian, M., Schröder, A., Scheel, B., Hong, H. S., Muth, A., von Boehmer, L., Zippelius, A., Mayer, F., Reck, M., Atanackovic, D., Thomas, M., Schneller, F., Stöhlmacher, J., Bernhard, H., Gröschel, A., Lander, T., Probst, J., Strack, T., Wiegand, V., ... Koch, S. D. (2019). A phase I/IIa study of the mRNA-based cancer immunotherapy CV9201 in patients with stage IIIB/IV non-small cell lung cancer. CANCER IMMUNOL IMMUN, 68(5), 799-812. https://doi.org/10.1007/s00262-019-02315-x

Vancouver

Sebastian M, Schröder A, Scheel B, Hong HS, Muth A, von Boehmer L et al. A phase I/IIa study of the mRNA-based cancer immunotherapy CV9201 in patients with stage IIIB/IV non-small cell lung cancer. CANCER IMMUNOL IMMUN. 2019 May;68(5):799-812. https://doi.org/10.1007/s00262-019-02315-x

Bibtex

@article{5ffc58e7744349ca885d2fa931aaad0e,
title = "A phase I/IIa study of the mRNA-based cancer immunotherapy CV9201 in patients with stage IIIB/IV non-small cell lung cancer",
abstract = "CV9201 is an RNActive{\textregistered}-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 = "Aged, Aged, 80 and over, Antigens, Neoplasm/genetics, B-Lymphocytes/immunology, Cancer Vaccines/genetics, Carcinoma, Non-Small-Cell Lung/immunology, Cells, Cultured, Female, Humans, Immunotherapy/adverse effects, Injection Site Reaction/etiology, Lung Neoplasms/immunology, Lymphocyte Activation, Male, Middle Aged, Neoplasm Staging, RNA, Messenger/administration & dosage, Survival Analysis, T-Lymphocytes/immunology",
author = "Martin Sebastian and Andreas Schr{\"o}der and Birgit Scheel and Hong, {Henoch S} and Anke Muth and {von Boehmer}, Lotta and Alfred Zippelius and Frank Mayer and Martin Reck and Djordje Atanackovic and Michael Thomas and Folker Schneller and Jan St{\"o}hlmacher and Helga Bernhard and Andreas Gr{\"o}schel and Thomas Lander and Jochen Probst and Tanja Strack and Volker Wiegand and Ulrike Gnad-Vogt and Karl-Josef Kallen and Ingmar Hoerr and {von der Muelbe}, Florian and Mariola Fotin-Mleczek and Alexander Knuth and Koch, {Sven D}",
year = "2019",
month = may,
doi = "10.1007/s00262-019-02315-x",
language = "English",
volume = "68",
pages = "799--812",
journal = "CANCER IMMUNOL IMMUN",
issn = "0340-7004",
publisher = "Springer Science and Business Media Deutschland GmbH",
number = "5",

}

RIS

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 -