Details

Autor(en) / Beteiligte

• 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

Titel

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

Ist Teil von

• Journal for immunotherapy of cancer, 2019-02, Vol.7 (1), p.38-14, Article 38

Ort / Verlag

England: BioMed Central Ltd

Erscheinungsjahr

2019

Quelle

Elektronische Zeitschriftenbibliothek - Freely accessible e-journals

Beschreibungen/Notizen

• 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. 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). 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. The results support further investigation of mRNA-based immunotherapy in NSCLC including combinations with immune checkpoint inhibitors. ClinicalTrials.gov identifier: NCT01915524 .