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
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 620
- 试验地点
- 28
- 主要终点
- Objective Response Rate (ORR) at Week 18
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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)
排除标准
- •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
研究组 & 干预措施
Bevacizumab with Paclitaxel and Carboplatin
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.
干预措施: Bevacizumab (Drug)
Bevacizumab with Paclitaxel and Carboplatin
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.
干预措施: Paclitaxel (Drug)
Bevacizumab with Paclitaxel and Carboplatin
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.
干预措施: Carboplatin (Drug)
Avastin® with Paclitaxel and Carboplatin
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.
干预措施: Bevacizumab (Drug)
Avastin® with Paclitaxel and Carboplatin
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.
干预措施: Paclitaxel (Drug)
Avastin® with Paclitaxel and Carboplatin
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.
干预措施: Carboplatin (Drug)
结局指标
主要结局
Objective Response Rate (ORR) at Week 18
时间窗: 18 weeks from randomisation
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).
次要结局
- Progression-free Survival (PFS)(At week 18 and 42 from randomisation)
- Duration of response (DOR)(48 weeks)
- Overall Survival (OS)(At week 18 and 42 from randomisation)