Trial of RNActive®-Derived Cancer Vaccine and Local Radiation in in Stage IV Non Small Cell Lung Cancer (NSCLC)

Key Inclusion Criteria: 1. Patients \>= 18 years of age with histologically or cytologically-confirmed stage IV NSCLC, and a confirmed EGFR mutation status in case of non-squamous cell histology * Stratum 1: Non-squamous NSCLC without activating EGFR mutation * Stratum 2: Squamous NSCLC * Stratum 3: Non-squamous NSCLC harboring an activating EGFR mutation 2. PR or SD according to RECIST Version 1.1 after first-line therapy which should have consisted of: * Stratum 1: PR or SD after cisplatin or carboplatin and pemetrexed treatment (at least 4 cycles) * Stratum 2: PR or SD after cisplatin or carboplatin and a non-platinum compound treatment (at least 4 cycles) * Stratum 3: PR after up to 6 months or SD after at least 3 and up to 6 months of gefitinib or erlotinib treatment 3. For patients in stratum 1, maintenance therapy with pemetrexed should be indicated as to the investigator's opinion 4. Presence of at least one tumor lesion that is eligible for radiation with 4 x 5 GY, and at least one additional measurable tumor lesion according to RECIST Version 1.1. Tumor lesions eligible for radiation are: * Bone metastases * Lymph nodes in the paraclavicular, axillary or cervical regions * Skin or subcutaneous metastases * For patients in strata 1 and 2 only: Thoracic lesions (centrally located lung tumor, lymph nodes in the lung hilus or mediastinum) 5. Performance Status: Eastern Cooperative Oncology Group (ECOG) 0 to 1 Key Exclusion Criteria: 1. Previous active immunotherapy for NSCLC (including vaccination, therapy with anti-CTLA4 antibodies) 2. Estimated life expectancy ≤ 3 months 3. Need for immunosuppressive treatment including daily systemic steroid doses of ≥ 10 mg prednisone equivalent per day 4. Active skin disease (e.g. atopic dermatitis) in the areas for vaccine injection (upper arms or thighs) not allowing intradermal injections into areas of healthy skin 5. Concurrent or planned major surgery 6. Prior splenectomy or prior allogeneic bone marrow transplantation 7. History of pneumonitis 8. Documented history or active autoimmune disorders with the exception of vitiligo, diabetes mellitus type 1 or autoimmune thyroiditis requiring hormone replacement only 9. Primary or secondary immune deficiency 10. Allergies to any components of the study drug including allergy to protamine hydrochloride (e.g. allergy to protamine-containing insulin) or fish allergy 11. Seropositive for HIV, HBV, HCV or any other infection requiring anti-infection therapy 12. For patients in stratum 3: persisting \>= grade 3 skin rash at time of enrollment 13. Known brain metastases with the exception of stable metastases being treated with stereotactic radiation or surgery) \*\*Local German Amendment: 13. Brain metastases (symptomatic or asymptomatic) or leptomeningeal involvement 14. Uncontrolled medical condition considered as high risk for the treatment with an investigational drug (e.g. unstable diabetes mellitus, vena-cava-syndrome, uncontrolled pleural effusion, pericardial effusion, symptomatic congestive heart failure (New York Heart Association 3 or 4), unstable angina pectoris/myocardial infarction within the previous 6 months, significant cardiac arrhythmia, history of stroke or transient ischemic attack within the previous 6 months, severe hypertension according to WHO criteria, and uncontrolled systolic blood pressure ≥ 180 mmHg at the time of enrollment 15. For patients planned to undergo radiation of thoracic lesions: inadequate lung function dependent on the intended tumor volume and location to be irradiated (to be assessed by the radio oncologist) 16. History of encephalitis or multiple sclerosis 17. Active inflammatory conditions such as inflammatory bowel disease