A Study Comparing MB02 and Avastin® in Subjects With Stage IIIB/IV Non-Squamous Non-Small Cell Lung Cancer (NSCLC)

Inclusion Criteria

• Males and female subjects aged ≤ 18 years to ≤ 80 years.
• Signed informed consent must be obtained before initiation of any study-specific procedures or treatment as confirmation of the subject's awareness and willingness to comply with the study requirements.
• Subjects should have newly diagnosed or recurrent Stage IIIB/IV (defined by seventh edition of the Tumor, Node and Metastasis (TNM) classification for Lung Cancer, 2010) non-squamous NSCLC not amenable to curative intent surgery, and not have received any systemic therapy for advanced disease (exclusion criteria 3 and 4). For subjects with recurrent disease, at least 6 months must have elapsed before randomization from previous adjuvant treatment.
• Previous radiation therapy if completed >4 weeks before randomization. Palliative radiotherapy to bone lesions is allowed if completed >2 weeks of randomization.
• Subjects must have at least 1 unidimensional measurable lesion per RECIST version 1.1 (assessed locally).
• Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status ≤1 at Screening.
• Subjects must have adequate hepatic, renal and hematologic function defined as:
• Hepatic function: bilirubin level 50 mL/min (Cockcroft-Gault formula), urine protein to creatinine ratio 1 may be enrolled if they have 1.5×109 /L; platelets >100×109 /L, hemoglobin (Hb) >9 g/dL.
• Adequate coagulation parameters such as: INR ≤ 2.0 and aPTT ≤ 1.5 x ULN within 7 days prior to randomization for patients not receiving anticoagulation therapy.
• Eligible subjects must have a systolic blood pressure of ≤ 140 mm Hg and a diastolic blood pressure of ≤90 mm Hg at screening.
• Women of childbearing potential, and their partners, must agree to adhere to pregnancy prevention methods throughout the duration of the study (including the Follow-up visits, where applicable). Women of childbearing potential are defined as those who are not surgically sterile (did not underwent bilateral tubal ligation, bilateral oophorectomy, or hysterectomy) and not postmenopausal.

Subjects and their partners must agree to use a highly effective method of contraception, to avoid women becoming pregnant throughout the course of the study. Medically acceptable forms of birth control can include the following, with approval of the treating physician:

• Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, or transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomized partner, sexual abstinence.
• Non fertile women can be included, that is, those who are physiologically incapable of becoming pregnant, because of:
• Hysterectomy.
• Bilateral oophorectomy (ovariectomy).
• Bilateral tubal ligation or,
• Postmenopausal women defined as:

Subjects not using hormone replacement therapy (HRT) and have experienced total cessation of menses for ≥ 1 year and be greater than 45 years of age, OR, in questionable cases, have a follicle stimulating hormone >40 mIU/mL and an estradiol value 2, unless receiving active anticoagulation treatment, will be excluded.

• Subjects who have a diagnosis of small cell carcinoma of the lung or squamous cell carcinoma of the lung. Mixed tumors should be categorized according to the predominant histology. If small cell elements are present, the subject will be excluded.
• Subjects with known tumors that harbor activating epidermal growth factor receptor and anaplastic lymphoma receptor tyrosine kinase (assessed locally).
• Subjects who have a history of hypersensitivity to the active substance (bevacizumab, carboplatin, and/or paclitaxel) or any of the excipients (such as trehalose dehydrate, sodium phosphate, or polysorbate 20).
• Subjects with known active viral infection, including but no