<br>        Inclusion Criteria:<br><br>          -  Histological confirmed Non-Small-Cell lung cancer<br><br>          -  Tumor stage  IV (UICC 7th Version)<br><br>          -  The following histological tumor types are eligible:<br><br>               -  Adenocarcinoma (including adenocarcinomas with bronchioloalveolar<br>                  differentiation)<br><br>               -  Large Cell carcinoma without neuroendocrine differentiation<br><br>               -  Mixed Cell Carcinoma without small cell fraction and without predominant<br>                  squamous cell fraction<br><br>               -  undifferentiated non-small-cell-carcinoma<br><br>          -  No previous chemotherapy for stage IV NSCLC<br><br>          -  Adjuvant or neoadjuvant chemotherapy for NSCLC must be completed at least one year<br>             prior to study enrolment (from end of chemotherapy)<br><br>          -  No previous treatment with Pemetrexed or Bevacizumab<br><br>          -  Patients with prior radiation therapy may be eligible for this study if they meet the<br>             following guidelines:<br><br>               -  Previous radiation therapy is allowed to <25% of the bone marrow (Cristy and<br>                  Eckerman 1987), but should have been limited and must not have included whole<br>                  pelvis radiation.<br><br>               -  Patients must have recovered from the toxic effects of the treatment prior to<br>                  study enrollment (except for alopecia).<br><br>               -  Prior thoracic radiotherapy must be completed 30 days before study enrollment.<br><br>               -  Lesions that have been radiated cannot be included as sites of measurable<br>                  disease unless clear tumor progression has been documented in these lesions<br>                  since the end of radiation therapy.<br><br>               -  Palliative extrathoracic radiotherapy to preexisting lesions may continue on<br>                  study; however, these lesions may not be included as sites of measurable<br>                  disease.<br><br>          -  At least 4 weeks since last major surgery<br><br>          -  Age = 18  and  = 70 years<br><br>          -  ECOG = 1<br><br>          -  Adequate hematological laboratory parameters:<br><br>               -  Hemoglobin      =9 g/dl<br><br>               -  Neutrophils     = 1.500 µl<br><br>               -  WBC       =3.000 µl<br><br>               -  Platelets =100.000 µl<br><br>          -  Adequate hepatic laboratory parameters:<br><br>               -  Total Bilirubin      = 1,5 x ULN<br><br>               -  Alkaline phosphatase = 3 x ULN<br><br>               -  AST(GOT)   < 2,5 ULN in patients without liver metastasis < 5 x ULN in patients<br>                  with liver metastasis ULN = (upper limit of normal)<br><br>               -  ALT(GPT)   <  2,5 ULN in patients without liver metastasis <  5 x ULN in<br>                  patients with liver metastasis ULN = (upper limit of normal)<br><br>          -  Adequate renal laboratory parameters:<br><br>               -  Creatinine Clearance > 50 ml/min<br><br>               -  Urine dipstick for proteinuria < 2+ Patients discovered to have = 2+ proteinuria<br>                  on dipstick urinalysis at baseline should undergo a 24-hour urine collection and<br>                  must demonstrate <1 g of protein in 24 hours<br><br>          -  Normal cardiac function defined by New York Heart Association - NYHA Class I and<br>             Class II<br><br>          -  Electrocardiogram without significant signs of cardiac arrhythmias<br><br>          -  Provision of informed consent according to local regulatory requirements prior to any<br>             protocol specific treatment.<br><br>          -  Measurable lesion according to RECIST 1.1<br><br>          -  Negative pregnancy test for women of childbearing potential unless they are<br>             postmenopausal at baseline. (Postmenopausal women must have been amenorrheic at least<br>             for 12 months to be considered of non childbearing potential)<br><br>          -  Women of child bearing potential to be willing to use an acceptable method to avoid<br>             pregnancy at least one month before study start. Examples: oral contraceptives (sole<br>             application of oral contraceptives is not sufficient), diaphragm pessary,<br>             intrauterine device (spiral), condom plus diaphragm pessary plus spermicide.<br><br>        Exclusion Criteria:<br><br>          -  Histological confirmed predominant squamous cell carcinoma<br><br>          -  Presence of activating EGFR mutations in exons 18-21<br><br>          -  Pregnancy or lactation period<br><br>          -  Have known central nervous system (CNS) disease, other than stable, treated brain<br>             metastasis.  Stable, treated brain metastasis is defined as metastasis having no<br>             evidence of progression or hemorrhage after treatment and no ongoing requirement for<br>             dexamethasone, as ascertained by clinical examination and post-treatment brain<br>             imaging (CT scan or magnetic resonance imaging [MRI]).  Patients should be off<br>             corticosteroids for 1 week (7 days) at the time of the post-treatment brain CT/MRI.<br>             Anticonvulsants (stable dose) are allowed.  Treatment for brain metastases may<br>             include whole brain radiotherapy, (stereotactic) radiosurgery (Gamma Knife, linear<br>             particle accelerator, or equivalent), or a combination as deemed appropriate by the<br>             treating physician, and must have been completed > 8 days prior to Day 1 of Cycle 1.<br>             Patients with signs of a fresh bleeding into one or more cerebral metastases  or with<br>             CNS metastases treated by neurosurgical resection or brain biopsy performed within 8<br>             weeks prior to Day 1 of Cycle 1 will be excluded.<br><br>          -  Evidence of tumor invading or abutting major blood vessels<br><br>          -  Presence of a tracheobronchial fistula<br><br>          -  History of abdominal fistula or fistulisation of urogenital tract, gastrointestinal<br>             perforation or intra-abdominal abscess, inflammatory bowel disease, or diverticulitis<br>             within 6 months prior to study start<br><br>          -  Other co-existing malignancies or malignancies diagnosed within the last 5 years with<br>             the exception of a CIS of the cervix, non-melanomatous skin cancer, stable chronic<br>             lymphatic leukaemia, non-muscle invasive bladder cancer or surgically treated or<br>             irradiated prostate cancer with no signs of recurrence for one year. Patients with<br>             other malignancies curatively treated and free of disease for at least 5 years will<br>             be discussed with the Principal Investigator (LKP) before inclusion.<br><br>          -  Treatment with an investigational new drug, currently or within the last 28 days,<br>             and/or participation in another clinical trial, currently or during the last 12<br>             weeks, and/or previous participation in this study.<br><br>          -  History or presence of a mental disease or condition such as to interfere with the<br>             patient's ability to understand the requirements of the study and the intake of study<br>             medication according to study protocol.<br><br>          -  Patients with any clinically significant disease that in the opinion of the<br>             investigator is likely to put the patient at risk or to interfere with the evaluation<br>             of the patient's safety and of the study outcome. This includes, but is not limited<br>             to:<br><br>               -  Immed