A Safety and Efficacy Study of BCD-021 With Paclitaxel and Carboplatin Compared to Avastin With Paclitaxel and Carboplatin in Non-Small Cell Lung Cancer

International Multicenter Randomized Double Blind Phase III Trial Comparing Safety and Efficacy of BCD-021 (CJSC BIOCAD, Russia) and Paclitaxel + Carboplatin to Avastin® (F. Hoffmann-La Roche Ltd, Switzerland) and Paclitaxel + Carboplatin in Inoperable or Advanced Non-squamous Non-small-cell Lung Cancer (NSCLC) Patients

BCD-021-02 is a double-blind randomized clinical trial comparing efficacy of BCD-021 (INN: bevacizumab) and paclitaxel + carboplatin to Avastin and paclitaxel + carboplatin in inoperable or advanced non-squamous NSCLC patients with pharmacokinetics substudy. The purpose of the study is to demonstrate the non-inferiority of efficacy and safety of BCD-021 compared to Avastin. Also study includes pharmacokinetics assessment.

Inclusion Criteria:

• Written informed consent;
• Newly diagnosed histologically or cytologically confirmed NSCLC excluding squamous NSCLC (mixed cancer types should be classified according to the prevalent cell type);
• IIIb or IV stage of NSCLC (TNM classification version 6);
• Age ≥ 18 years and age ≤ 75 years (both inclusive);
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2, (not declining within 2 weeks prior to the first dose of investigational product);
• Life expectancy - 12 weeks or more from the moment of randomization;
• Presence of at least 1 measurable tumour with a size not less than 1 cm (revealed with CT slice thickness not more than 5 mm), as defined by modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria (specifically, no ascites, pleural, or pericardial effusions, osteoblastic bone metastases, or carcinomatous lymphangitis of the lung as only lesion;
• Patients should be able to follow the Protocol procedures (according to Investigator's assessment);
• Patients must implement reliable contraceptive measures during all the study treatment, starting 4 weeks prior to the administration of the first dose of investigational product until 6 months after the last dose of investigational product. This requirement does not apply to participants who have undergone surgical sterilization, or patients who are postmenopausal (documented) for the past 2 years. Reliable contraceptive measures include two methods of contraception, including one barrier method

Exclusion Criteria:

• Squamous NSCLC;
• Proven coagulopathy, clinically significant hemorrhage in the past including nasal hemorrhage;
• absolute neutrophil count <1500/mm3;
• Platelets <100 000/mm3;
• Hemoglobin < 90 g/L;
• Creatinine level ≥1.5 mg/dL;
• Bilirubin level ≥1.5 × upper limit of normal (ULN);
• Aspartate-aminotransferase(AST) and alanine-aminotransferase (ALT) levels ≥2.5 × ULN (≥5 × ULN for patients with liver metastases);
• Alkaline phosphatase level ≥5 × ULN;
• Current therapeutic anticoagulation treatment, aspirin (more than 325 mg/day), nonsteroidal anti-inflammatory drugs, antiplatelet agents or protracted treatment with these drugs less than 1 month before entering the study;
• Uncontrolled hypertension comprising all cases of arterial hypertension when no decrease in blood pressure could be achieved despite treatment with a combination of 3 antihypertensive drugs including one diuretic and non-medical correction methods (low salt diet, physical exercise);
• Any previous anticancer therapy (chemotherapy, radiation therapy , surgery etc.) of metastatic NSCLC;
• Radiation or hormone therapy within 21 days prior to randomization;
• Major surgery 28 days before inclusion into the study;
• Previous antiangiogenic therapy;
• Hypersensitivity to taxanes, platinum agents, recombinant murine proteins, contrast agents, premedication agents specified by Protocol (dexamethasone, diphenhydramine, ranitidine) or excipients of investigational products;
• NSCLC metastases in central nervous system excluding metastases non-progressing without glucocorticosteroids within 4 weeks before inclusion into the trial;
• Cardiovascular system pathology (CHF stage III-IV according to New York Heart Association (NYHA) classification);
• Pregnancy or lactation;
• Conditions limiting patient's adherence to Protocol requirements (dementia, neurologic or psychiatric disorders, drug addiction, alcoholism and others);
• Stage II-IV neuropathy according to Common Terminology Criteria for Adverse Events (CTCAE) v.4.0;
• Simultaneous participation in other clinical trials, previous participation in other clinical trials within 30 days before entering into the trial, previous participation in the same trial;
• Any other concomitant cancer revealed within 5 years prior to screening, except curatively treated intraductal carcinoma in situ, curatively treated cervical carcinoma in situ or curatively treated basal cell or squamous cell carcinoma;
• Acute or active chronic infections;
• Hepatitis C virus, hepatitis B virus, HIV, or syphilis infections;
• Obstacles in intravenous administration of study drugs