A Safety and Efficacy Study of Bevacizumab, Paclitaxel, Carboplatin Compared to Avastin® in Non-Small Cell Lung Cancer

Randomized Double Blind Phase III Trial Comparing Safety and Efficacy of Bevacizumab (Mabscale LLC, Russia) + Paclitaxel + Carboplatin to Avastin® + Paclitaxel + Carboplatin in Inoperable or Advanced Non-squamous Non-small-cell Lung Cancer

BEV-III/2022 is a double-blind randomized multicenter clinical trial comparing efficacy of bevacizumab (manufactured by Mabscale, LLC) and paclitaxel plus carboplatin to Avastin® and paclitaxel plus carboplatin in first-line treatment for patients with advanced (unresectable, locally advanced, recurrent or metastatic) non-squamous NSCLC. The purpose of the study is to demonstrate equivalence of efficacy and safety of bevacizumab (manufactured by Mabscale, LLC) to Avastin®. Study includes pharmacokinetics assessment.

Bevacizumab is a monoclonal antibody currently being developed by Mabscale LLC, as a proposed biosimilar to Avastin®, which is approved as first line treatment in combination with carboplatin and paclitaxel for patients with unresectable, locally advanced, recurrent or metastatic non-squamous Non-Small Cell Lung Cancer. This randomized equivalence study is designed to meet the regulatory requirement for approval of a biosimilar product.

Inclusion Criteria:

• Written informed consent
• Male and female patients at least 18 years of age
• Newly diagnosed Stage IIIB/C or IV non-small cell lung cancer (according to Revised Cancer Staging by American Joint Committee on Cancer (AJCC) and the International Union Against Cancer (UICC) 8th edition) or recurrent non-small cell lung cancer (NSCLC)
• Histologically or cytologically confirmed diagnosis of predominately non-squamous NSCLC
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Be eligible to receive study treatment of bevacizumab, paclitaxel, and carboplatin based on local standard of care, for the treatment of advanced or metastatic non-squamous NSCLC
• Presence of at least 1 measurable tumour as defined by modified Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
• Neutrophils ≥ 1,5 × 10^9/L
• Platelets ≥ 100 × 10^9/L
• Haemoglobin ≥ 90 g/L
• Bilirubin level ≤ 1.5 × upper limit of normal (ULN)
• Aspartate-aminotransferase (AST) and alanine-aminotransferase (ALT) levels < 3 × ULN (< 5 × ULN for patients with liver metastases)
• Alkaline phosphatase level < 3 × ULN (< 5 × ULN for patients with liver or bone metastases)

Exclusion Criteria:

• Known sensitizing EGFR mutations or ALK translocation positive mutations
• Evidence of a tumor that compresses or invades major blood vessels or tumor cavitation that is likely to bleed
• Major surgery 28 days before inclusion into the study
• Minor surgery 7 days before inclusion into the study
• Stage II or higher of neuropathy or ototoxicity according to Common Terminology Criteria for Adverse Events (CTCAE) v.5.0, excluding trauma
• Life expectancy less than 6 months
• Metastases to central nervous system or carcinomatous meningitis
• Pregnancy or lactation