<> "The repository administrator has not yet configured an RDF license."^^ . <> . . . "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"^^ . "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.\r\n\r\nMethods: 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).\r\n\r\nResults: 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 involvement of multiple antigen specificities was evident in 52% of patients. One patient had a partial response in combination with pemetrexed maintenance, and 46.2% achieved stable disease as best overall response. Best overall response was SD in 57.7% for target lesions.\r\n\r\nConclusion: The results support further investigation of mRNA-based immunotherapy in NSCLC including combinations with immune checkpoint inhibitors.\r\n\r\nTrial registration: ClinicalTrials.gov, Identifier: NCT01915524."^^ . "2019" . . "7" . "38" . . "BioMed Central"^^ . . . "Journal for ImmunoTherapy of Cancer"^^ . . . "20511426" . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . "Anke"^^ . "Muth"^^ . "Anke Muth"^^ . . "Ulrike"^^ . "Gnad-Vogt"^^ . "Ulrike Gnad-Vogt"^^ . . "Miklos"^^ . "Pless"^^ . "Miklos Pless"^^ . . "Wolfgang"^^ . "Hilbe"^^ . "Wolfgang Hilbe"^^ . . "Claudia"^^ . "Stosnach"^^ . "Claudia Stosnach"^^ . . "Alexandros"^^ . "Papachristofilou"^^ . "Alexandros Papachristofilou"^^ . . "Martin"^^ . "Sebastian"^^ . "Martin Sebastian"^^ . . "Henoch S."^^ . "Hong"^^ . "Henoch S. Hong"^^ . . "Mariola"^^ . "Fotin-Mleczek"^^ . "Mariola Fotin-Mleczek"^^ . . "Frank"^^ . "Griesinger"^^ . "Frank Griesinger"^^ . . "Andreas"^^ . "Schröder"^^ . "Andreas Schröder"^^ . . "Birgit"^^ . "Scheel"^^ . "Birgit Scheel"^^ . . "Helge"^^ . "Bischoff"^^ . "Helge Bischoff"^^ . . "Madeleine M."^^ . "Hipp"^^ . "Madeleine M. Hipp"^^ . . "Martin"^^ . "Früh"^^ . "Martin Früh"^^ . . "Christian"^^ . "Weiss"^^ . "Christian Weiss"^^ . . "Fatma"^^ . "Doener"^^ . "Fatma Doener"^^ . . "Jürgen"^^ . "Alt"^^ . "Jürgen Alt"^^ . . "Richard"^^ . "Cathomas"^^ . "Richard Cathomas"^^ . . "Alfred"^^ . "Zippelius"^^ . "Alfred Zippelius"^^ . . "Sven D."^^ . "Koch"^^ . "Sven D. Koch"^^ . . "Michael"^^ . "Geißler"^^ . "Michael Geißler"^^ . . "Karl-Josef"^^ . "Kallen"^^ . "Karl-Josef Kallen"^^ . . "Georg"^^ . "Pall"^^ . "Georg Pall"^^ . . "Thomas"^^ . "Wehler"^^ . "Thomas Wehler"^^ . . "Ute"^^ . "Klinkhardt"^^ . "Ute Klinkhardt"^^ . . "Tobias"^^ . "Seibel"^^ . "Tobias Seibel"^^ . . . . . . "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 (PDF)"^^ . . . "40425_2019_Article_520.pdf"^^ . . . 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"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 (Other)"^^ . . . . . . "small.jpg"^^ . . . "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 (Other)"^^ . . . . . . "indexcodes.txt"^^ . . "HTML Summary of #26070 \n\nPhase 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\n\n" . "text/html" . . . "610 Medizin"@de . "610 Medical sciences Medicine"@en . .