A Trial to Compare the Efficacy, Safety, Pharmacokinetics and Immunogenicity of HD204 to Avastin® in Advanced Non-squamous Non-small Cell Lung Cancer Patients

Study Overview
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Brief Summary
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In the SAMSON-2 study, the proposed biosimilar HD204 will be compared to its reference product EU-licensed Avastin®. The aim of the study is to demonstrate equivalence of HD204 and EU-licensed Avastin® in terms of efficacy, safety, pharmacokinetics and immunogenicity.

Detailed Description
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This is a randomised, double-blind, parallel group, equivalence, multicentre Phase III study in patients with metastatic or recurrent non-squamous non-small cell lung cancer (NSCLC). Standard efficacy parameters, safety profiles, pharmacokinetics and immunogenicity will be compared between HD204 and bevacizumab.

Official Title
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A Randomised, Double-blind, Parallel Group, Equivalence, Multicentre Phase III Trial to Compare the Efficacy, Safety, Pharmacokinetics and Immunogenicity of HD204 to Avastin® in Patients 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: HD204
* 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 |
| --- | --- |
| Experimental: HD204 (Bevacizumab biosimilar)<br>HD204 + Carboplatin/Paclitaxel | Drug: HD204<br>* 15 mg/kg IV every 3 weeks on Day 1<br>* Other names: Bevacizumab;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;|
| Active Comparator: Avastin (Bevacizumab)<br>Avastin® + Carboplatin/Paclitaxel | Drug: Bevacizumab<br>* 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;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) at Week 18 | Percent patients within each treatment group who achieved complete response (CR) or partial response (PR) by the time of the Week 18 efficacy analysis in accordance with the RECIST 1.1. as assessed by CIR. | 18 weeks from randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR at Week 6 | Response at Week 6 will be evaluated by CIR to show the pattern of response | 6 weeks from randomization | 
| ORR at Week 12 | Response at Week 12 will be evaluated by CIR to show the pattern of response | 12 weeks from randomization | 
| ORR at Week 18 adjusted on dose intensity | To compare ORR at Week 18 adjusted on dose intensity between treatment groups | 18 weeks from randomization | 
| 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 | 
| Progression Free Survival | PFS from the date of randomisation to the date of disease progression or death up to 12 months from randomisation | 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) | OS defined as the time from Day 1 of therapy until death from any cause | From the date of randomisation to the date of death up to 12 months from randomisation | 
| Change in tumour burden from baseline | Measured by the sum of longest diameters (SLD) of the target lesions | Up to 52 weeks from baseline | 
| Incidence of Treatment-related Adverse Events using CTCAE v5.0 | After the end of treatment (EOT) visit, SAEs should be reported to the Sponsor if the Investigator becomes aware of them. | From signing the ICF until 1 month after the last administration of treatment, i.e., up to 52 weeks | 
| Anti-Drug Antibodies (Immunogenicity) | Incidence of anti-drug (bevacizumab) antibodies (ADA) | Up to 52 weeks (at Baseline; end of Cycle 4 [pre-dose in cycle 5]; end of Cycle 7 [pre-dose in cycle 8]; and at EOT) | 
| Neutralizing Antibodies (Immunogenicity) | Incidence of anti-drug (bevacizumab) antibodies (ADA) - neutralizing antibodies (NAb) | Up to 52 weeks (at Baseline; end of Cycle 4 [predose in cycle 5]; end of Cycle 7 [predose in cycle 8]; and at EOT) | 
| Trough Level [Ctrough] (Pharmacokinetics) | Concentration observed 19 to 23 days after study drug administration | Up to 52 weeks (end of Cycle 1 [predose of Cycle 2], end of Cycle 3 [predose of Cycle 4], end of Cycle 5 [predose of Cycle 6] and EOT) | 
| Maximum Plasma Concentration [Cmax] (Pharmacokinetics) | Cmax at selected cycles | Up to 21 weeks (Cycle 2 ,4 and 6. Each cycle is 21 days.) | 
| Area under the concentration-time curve from 0 hr to time t [AUC0-t] (Pharmacokinetics) | AUC0-t at selected cycles | Up to 21 weeks (Cycle 2 ,4 and 6. Each cycle is 21 days.) |