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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Bevacizumab
* Drug: Paclitaxel
* Drug: Carboplatin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bevacizumab with Paclitaxel and Carboplatin<br>Patients will begin Period 1 receiving bevacizumab combination therapy (Bevacizumab 15 mg/kg IV + Paclitaxel 175 mg/m2 + IV Carboplatin AUC 6 IV) on Day 0 of Cycle 1 for up to 6 cycles of therapy. Each cycle will consist of 3 weeks (21 days ± 3 days) and a cycle will start with the administration of bevacizumab (produced by Mabscale, LLC). In Period 2, eligible patients will continue to receive bevacizumab (produced by Mabscale, LLC) every 3 weeks as monotherapy. | Drug: Bevacizumab<br>* Bevacizumab 15 mg/kg<br>Drug: Paclitaxel<br>* Paclitaxel 175 mg/m2<br>Drug: Carboplatin<br>* Carboplatin AUC 6<br>|
| Active Comparator: Avastin® with Paclitaxel and Carboplatin<br>Patients will begin Period 1 receiving bevacizumab combination therapy ( Avastin® 15 mg/kg IV + Paclitaxel 175 mg/m2 IV + Carboplatin AUC 6 IV) on Day 0 of Cycle 1 for up to 6 cycles of therapy. Each cycle will consist of 3 weeks (21 days ± 3 days) and a cycle will start with the administration of bevacizumab (as Avastin®). In Period 2, eligible patients will continue to receive bevacizumab (Avastin®) every 3 weeks as monotherapy. | Drug: Bevacizumab<br>* Bevacizumab 15 mg/kg<br>Drug: Paclitaxel<br>* Paclitaxel 175 mg/m2<br>Drug: Carboplatin<br>* Carboplatin AUC 6<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) at Week 18 | Objective response rate was assigned for a subject if the subject displayed either complete response (CR) or partial response (PR) per RECIST version 1.1 at Week 18, as assessed by independent radiological review committee (IRC). | 18 weeks from randomisation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) | Progression-free survival was defined as the time from randomization to subsequent confirmed progression per RECIST version 1.1, or death (whichever occurred first), measured in weeks and months. For PFS assessment clinical progression (i.e., treatment discontinuation due to progression of disease) was also considered as an event. | At week 18 and 42 from randomisation | 
| Overall Survival (OS) | Overall survival was defined as the time from randomization to subsequent death, measured in weeks and months. | At week 18 and 42 from randomisation | 
| Duration of response (DOR) | Duration of responce was defined as the time from responce to treatment till progression or death. | 48 weeks |