A Study Comparing SB8 and Avastin® in Patients With Advanced Non-squamous Non-small Cell Lung Cancer
- Conditions
- Lung CancerNon-small Cell Lung Cancer
- Interventions
- Registration Number
- NCT02754882
- Lead Sponsor
- Samsung Bioepis Co., Ltd.
- Brief Summary
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
Standard efficacy parameters, safety profiles, pharmacokinetics and immunogenicity will be compared between SB8 and bevacizumab.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 763
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Bevacizumab (Avastin) Bevacizumab Avastin® + Carboplatin/Paclitaxel Bevacizumab (Avastin) Carboplatin Avastin® + Carboplatin/Paclitaxel Bevacizumab (Avastin) Paclitaxel Avastin® + Carboplatin/Paclitaxel SB8 (A proposed bevacizumab biosimilar) SB8 SB8 + Carboplatin/Paclitaxel SB8 (A proposed bevacizumab biosimilar) Carboplatin SB8 + Carboplatin/Paclitaxel SB8 (A proposed bevacizumab biosimilar) Paclitaxel SB8 + Carboplatin/Paclitaxel
- Primary Outcome Measures
Name Time Method Percentage of Participants With Best Overall Response (Best Overall Response Rate[ORR]) by 24 Weeks 24 weeks from randomisation The best ORR was defined as the proportion of subjects whose best overall response was either Complete Response (CR) or Partial Response (PR) according to RECIST v1.1 during the induction treatment period by 24 weeks.
CR: Disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
- Secondary Outcome Measures
Name Time Method Progression Free Survival from the date of randomisation to the date of disease progression or death up to 12 months from randomisation of the last subject PFS is defined as the time from the date of Randomisation to the date of disease progression (progressive disease \[PD\]) or death regardless of the cause of death.
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).Overall Survival from the date of randomisation to the date of death up to 12 months from randomisation of the last subject OS was defined as the time from the date of randomisation to the date of death regardless of the cause of death.
Subjects who were alive at the time of analysis were censored at the date of last known alive.Duration of Response (DoR) from documented tumour response until disease progression up to 12 months from randomisation of the last subject DoR in subjects with response from documented tumour response until disease progression up to 12 months from randomisation of the last subject
Number of Participants With Treatment-related Adverse Events Using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v4.03 AEs were reported from the time the informed consent form (ICF) was signed until the EOT visit, approximately 24 months from study initiation. After the end of treatment (EOT) visit, SAEs should be reported to the Sponsor if the Investigator becomes aware of them.
Severity Grade of NCI-CTCAE v4.03 Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL) (Instrumental ADL refers to preparing meals, shopping for groceries or clothes, using the telephone, managing money, etc.) Grade 3: Severe or medically significant but not immediately life-threatening; hospitalisation or prolongation of hospitalisation indicated; disabling; limiting self-care ADL (Self-care ADL refer to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not bedridden.) Grade 4: Life-threatening consequences; urgent intervention indicated Grade 5: Death related to AEPharmacokinetics: Trough Level [Ctrough] Up to 21 weeks (Cycle 1,3,5 and 7. Each cycle is 21 days.) Ctrough at selected cycles (i.e., Cycle 1, 3, 5 and 7)
Pharmacokinetics: Maximum Plasma Concentration [Cmax] Up to 21 weeks (Cycle 1,3,5 and 7. Each cycle is 21 days.) Maximum Plasma Concentration (Cmax) at selected cycles (i.e., Cycle 1, 3, 5 and 7)
Immunogenicity Assessments (Anti-drug Antibodies) Up to 21 weeks (Cycle 1,3,5, 7 and EOT visit. Each cycle is 21 days.), approximately 24 months from study initiation. Incidence of anti-drug (bevacizumab) antibodies (ADA)
The incidence of overall ADA results (i.e. Positive, Negative, Inconclusive) was presented by treatment group at Cycle 7 and the end of treatment (EOT). Overall ADA result was defined as below:
* 'Positive' for a subject with treatment-induced or treatment-boosted ADA, where treatment-induced ADA indicated at least one positive result after pre-dose of Cycle 1 for subjects with negative ADA at pre-dose of Cycle 1, and treatment-boosted ADA indicated at least one positive result with higher titre level compared to pre-dose of Cycle 1 after pre-dose of Cycle 1 for subjects with positive ADA at pre-dose of Cycle 1.
* 'Negative' for a subject without positive ADA until Cycle 7 and EOT.
* 'Inconclusive' for a subject with positive ADA at Cycle 1 and without positive result with higher titre level observed after pre-dose of Cycle 1 up to Cycle 7 and EOT.Immunogenicity Assessments (Neutralizing Antibodies) Up to 21 weeks (Cycle 1,3,5, 7 and EOT visit. Each cycle is 21 days.), approximately 24 months from study initiation. Incidence of anti-drug (bevacizumab) antibodies (ADA) - neutralizing antibodies (NAb) The analysis was performed using the Safety Set (SAF). Overall Number of Participants Analyzed represents the number of subjects in SAF.
The total number is not the sum of the number of subjects of each visits, since NAb results only for subjects with ADA positive against SB8 or Avastin were used for the summary.
Number Analyzed of each visit is equal to the number of subjects with ADA positive of each visit, which is displayed in 8. Secondary Outcome: Immunogenicity Assessments (Anti-drug Antibodies).
Trial Locations
- Locations (104)
Brest Regional Oncology Dispensary
🇧🇾Brest, Belarus
Grodno Regional Clinical Hospital
🇧🇾Grodno, Belarus
N. N. Alexandrov Republican Scientific and Practical Center of Oncology and Medical Radiology
🇧🇾Lesnoy, Belarus
Minsk city Clinical Oncological Dispensary
🇧🇾Minsk, Belarus
Mogilev Regional Oncological Dispensary
🇧🇾Mogilev, Belarus
Vitebsk Regional Clinical Oncological Dispensary
🇧🇾Vitebsk, Belarus
JSC Maritime Hospital
🇬🇪Batumi, Georgia
JSC Saint Nikolozi Surgery Center
🇬🇪Kutaisi, Georgia
LTD Research Institute of Clinical Medicine
🇬🇪Tbilisi, Georgia
ICO-Institute of Clinical Oncology
🇬🇪Tbilisi, Georgia
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