This is an open-label, multicenter, 2-arm study to evaluate the safety and preliminary efficacy of the addition of a vaccine therapy to 1 or 2 checkpoint inhibitors for NSCLC.
Arm A: messenger ribonucleic acid (mRNA) Vaccine [BI 1361849 (formerly CV9202)] + anti-programmed death ligand 1 (PD-L1) antibody [durvalumab]
Arm B: messenger ribonucleic acid (mRNA) Vaccine [BI 1361849] + anti-programmed death ligand 1 (PD-L1) [durvalumab] + anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody [tremelimumab]
The run-in evaluation phase is followed by an expansion phase in which the cohort is expanded to 20 subjects (inclusive of subjects from the run-in).

Start Date20 Dec 2017

Sponsor / Collaborator

Ludwig Institute for Cancer Research Ltd.

[+4]

100 Clinical Results associated with MAGEC2 x NY-ESO-1 x MUC1 x survivin x MAGEC1 x 5T4

100 Translational Medicine associated with MAGEC2 x NY-ESO-1 x MUC1 x survivin x MAGEC1 x 5T4

0 Patents (Medical) associated with MAGEC2 x NY-ESO-1 x MUC1 x survivin x MAGEC1 x 5T4

Literatures (Medical) associated with MAGEC2 x NY-ESO-1 x MUC1 x survivin x MAGEC1 x 5T4

01 Dec 2019·Journal for ImmunoTherapy of CancerQ2 · MEDICINE

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

Q2 · MEDICINE

ArticleOA

Author: Fotin-Mleczek, Mariola ; Wehler, Thomas ; Sebastian, Martin ; Koch, Sven D ; Griesinger, Frank ; Gnad-Vogt, Ulrike ; Alt, Jürgen ; Geißler, Michael ; Schröder, Andreas ; Stosnach, Claudia ; Seibel, Tobias ; Pless, Miklos ; Doener, Fatma ; Muth, Anke ; Weiss, Christian ; Papachristofilou, Alexandros ; Cathomas, Richard ; Scheel, Birgit ; Bischoff, Helge ; Hipp, Madeleine M ; Hong, Henoch S ; Kallen, Karl-Josef ; Zippelius, Alfred ; Klinkhardt, Ute ; Früh, Martin ; Pall, Georg ; Hilbe, Wolfgang

BACKGROUNDPreclinical 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.METHODSWe 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).RESULTSStudy 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.CONCLUSIONThe results support further investigation of mRNA-based immunotherapy in NSCLC including combinations with immune checkpoint inhibitors.TRIAL REGISTRATIONClinicalTrials.gov identifier: NCT01915524 .

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