A Study Comparing SB8 and Avastin® in Patients With Advanced Non-squamous Non-small Cell Lung Cancer

Study Overview
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Brief Summary
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This study is designed to establish biosimilarity of SB8, a proposed biosimilar product of bevacizumab, to EU-sourced bevacizumab, in patients with metastatic or recurrent non-squamous non-small cell lung cancer (NSCLC).

Detailed Description
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Standard efficacy parameters, safety profiles, pharmacokinetics and immunogenicity will be compared between SB8 and bevacizumab.

Official Title
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A Phase 3, Randomised, Double-blind Study to Compare the Efficacy, Safety, PK and Immunogenicity Between SB8 (Proposed Bevacizumab Biosimilar) and Avastin® in Subjects With Metastatic or Recurrent Non-squamous Non-small Cell Lung Cancer

Conditions
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Lung Cancer, Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: Bevacizumab
* Drug: SB8
* Drug: Carboplatin
* Drug: Paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged ≥ 18 years ECOG performance status of 0-1 Histologically-confirmed metastatic or recurrent non-squamous non-small cell lung cancer At least one measurable lesion according to RECIST v1.1. Able to receive bevacizumab, carboplatin and paclitaxel based on adequate laboratory and clinical parameters Exclusion Criteria: Diagnosis of small cell carcinoma of the lung or squamous cell carcinoma Sensitizing EGFR mutations or ALK rearrangements Increased risk of bleeding determined by investigator based on radiographic / clinical findings History of systemic chemotherapy administered in the first-line setting for metastatic or recurrent disease of NSCLC.

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Bevacizumab (Avastin)<br>Avastin® + Carboplatin/Paclitaxel | Drug: Bevacizumab<br>* Avastin® 15 mg/kg IV every 3 weeks on Day 1<br>* Other names: Avastin®;Drug: Carboplatin<br>* Carboplatin AUC 6 IV every 3 weeks on Day 1 for 4-6 cycles<br>Drug: Paclitaxel<br>* Paclitaxel 200 mg/m2 IV every 3 weeks on Day 1 for 4-6 cycles<br>* Other names: Taxol;|
| Experimental: SB8 (A proposed bevacizumab biosimilar)<br>SB8 + Carboplatin/Paclitaxel | Drug: SB8<br>* SB8 15 mg/kg IV every 3 weeks on Day 1<br>* Other names: SB8 (A proposed bevacizumab biosimilar);Drug: Carboplatin<br>* Carboplatin AUC 6 IV every 3 weeks on Day 1 for 4-6 cycles<br>Drug: Paclitaxel<br>* Paclitaxel 200 mg/m2 IV every 3 weeks on Day 1 for 4-6 cycles<br>* Other names: Taxol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Objective Response Rate by 24 weeks | Any PR or CR prior to the 24th week will be marked as response | 24 weeks from randomisation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival | PFS from the date of randomisation to the date of disease progression or death up to 12 months from randomisation of the last subject | from the date of randomisation to the date of disease progression or death up to 12 months from randomisation of the last subject | 
| Overall Survival | OS from the date of randomisation to the date of death up to 12 months from randomisation of the last subject | from the date of randomisation to the date of death up to 12 months from randomisation of the last subject | 
| Duration of Response | DoR in subjects with response from documented tumour response until disease progression up to 12 months from randomisation of the last subject | from documented tumour response until disease progression up to 12 months from randomisation of the last subject | 
| Incidence of Treatment-related Adverse Events using CTCAE v4.03 | After the end of treatment (EOT) visit, SAEs should be reported to the Sponsor if the Investigator becomes aware of them. | AEs will be reported from the time the informed consent form (ICF) is signed until the EOT visit. The expected EOT visit for a final subject is approximately 30 months from study initiation. | 
| Pharmacokinetics: Trough Level [Ctrough] | Ctrough at selected cycles | Up to 21 weeks (Cycle 1,3,5 and 7. Each cycle is 21 days.) | 
| Pharmacokinetics: Maximum Plasma Concentration [Cmax] | Cmax at selected cycles | Up to 21 weeks (Cycle 1,3,5 and 7. Each cycle is 21 days.) | 
| Immunogenicity Assessments (Anti-drug Antibodies) | Incidence of anti-drug (bevacizumab) antibodies (ADA) | Up to 21 weeks (Cycle 1,3,5, 7 and EOT visit. Each cycle is 21 days. The expected EOT visit for a final subject is approximately 30 months from study initiation.) | 
| Immunogenicity Assessments (Neutralizing Antibodies) | Incidence of anti-drug (bevacizumab) antibodies (ADA) - neutralizing antibodies (NAb) | Up to 21 weeks (Cycle 1,3,5, 7 and EOT visit. Each cycle is 21 days. The expected EOT visit for a final subject is approximately 30 months from study initiation.) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NSCLC, bevacizumab, avastin