| Title: |
Phase Ib evaluation of a self-adjuvanted protamine formulated mRNA-based active cancer immunotherapy, BI1361849 (CV9202), combined with local radiation treatment in patients with stage IV non-small cell lung cancer |
| Authors: |
Papachristofilou, Alexandros; Hipp, Madeleine M.; Klinkhardt, Ute; Früh, Martin; Sebastian, Martin; Weiss, Christian; Pless, Miklos; Cathomas, Richard; Hilbe, Wolfgang; Pall, Georg; Wehler, Thomas; Alt, Jürgen; Bischoff, Helge; Geißler, Michael; Griesinger, Frank; Kallen, Karl-Josef; Fotin-Mleczek, Mariola; Schröder, Andreas; Scheel, Birgit; Muth, Anke; Seibel, Tobias; Stosnach, Claudia; Doener, Fatma; Hong, Henoch S.; Koch, Sven D.; Gnad-Vogt, Ulrike; Zippelius, Alfred |
| Publisher Information: |
BioMed Central |
| Publication Year: |
2019 |
| Collection: |
Heidelberg University: HeiDok |
| Subject Terms: |
ddc-610; 610 Medical sciences Medicine |
| Description: |
Background: Preclinical studies demonstrate synergism between cancer immunotherapy and local radiation, enhancing anti-tumor effects and promoting immune responses. BI1361849 (CV9202) is an active cancer immunotherapeutic comprising protamine-formulated, sequence-optimized mRNA encoding six non-small cell lung cancer (NSCLC)-associated antigens (NY-ESO-1, MAGE-C1, MAGE-C2, survivin, 5T4, and MUC-1), intended to induce targeted immune responses. Methods: We describe a phase Ib clinical trial evaluating treatment with BI1361849 combined with local radiation in 26 stage IV NSCLC patients with partial response (PR)/stable disease (SD) after standard first-line therapy. Patients were stratified into three strata (1: non-squamous NSCLC, no epidermal growth factor receptor (EGFR) mutation, PR/SD after ≥4 cycles of platinum- and pemetrexed-based treatment [n = 16]; 2: squamous NSCLC, PR/SD after ≥4 cycles of platinum-based and non-platinum compound treatment [n = 8]; 3: non-squamous NSCLC, EGFR mutation, PR/SD after ≥3 and ≤ 6 months EGFR-tyrosine kinase inhibitor (TKI) treatment [n = 2]). Patients received intradermal BI1361849, local radiation (4 × 5 Gy), then BI1361849 until disease progression. Strata 1 and 3 also had maintenance pemetrexed or continued EGFR-TKI therapy, respectively. The primary endpoint was evaluation of safety; secondary objectives included assessment of clinical efficacy (every 6 weeks during treatment) and of immune response (on Days 1 [baseline], 19 and 61). Results: Study treatment was well tolerated; injection site reactions and flu-like symptoms were the most common BI1361849-related adverse events. Three patients had grade 3 BI1361849-related adverse events (fatigue, pyrexia); there was one grade 3 radiation-related event (dysphagia). In comparison to baseline, immunomonitoring revealed increased BI1361849 antigen-specific immune responses in the majority of patients (84%), whereby antigen-specific antibody levels were increased in 80% and functional T cells in 40% of patients, and ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| ISSN: |
2051-1426 |
| Relation: |
https://archiv.ub.uni-heidelberg.de/volltextserver/26070/1/40425_2019_Article_520.pdf; urn:nbn:de:bsz:16-heidok-260704; Papachristofilou, Alexandros; Hipp, Madeleine M.; Klinkhardt, Ute; Früh, Martin; Sebastian, Martin; Weiss, Christian; Pless, Miklos; Cathomas, Richard; Hilbe, Wolfgang; Pall, Georg; Wehler, Thomas; Alt, Jürgen; Bischoff, Helge; Geißler, Michael; Griesinger, Frank; Kallen, Karl-Josef; Fotin-Mleczek, Mariola; Schröder, Andreas; Scheel, Birgit; Muth, Anke; Seibel, Tobias; Stosnach, Claudia; Doener, Fatma; Hong, Henoch S.; Koch, Sven D.; Gnad-Vogt, Ulrike; Zippelius, Alfred (2019) Phase Ib evaluation of a self-adjuvanted protamine formulated mRNA-based active cancer immunotherapy, BI1361849 (CV9202), combined with local radiation treatment in patients with stage IV non-small cell lung cancer. Journal for ImmunoTherapy of Cancer, 7 (38). pp. 1-14. ISSN 2051-1426 |
| Availability: |
https://archiv.ub.uni-heidelberg.de/volltextserver/26070/ |
| Rights: |
info:eu-repo/semantics/openAccess ; Please see front page of the work (Sorry, Dublin Core plugin does not recognise license id) |
| Accession Number: |
edsbas.E0E7486 |
| Database: |
BASE |