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)
E-Da Hospital
🇨🇳Kaohsiung, Taiwan
Brest Regional Oncology Dispensary
🇧🇾Brest, Belarus
LTD Research Institute of Clinical Medicine
🇬🇪Tbilisi, Georgia
Grodno Regional Clinical Hospital
🇧🇾Grodno, Belarus
Minsk city Clinical Oncological Dispensary
🇧🇾Minsk, Belarus
Klinik Löwenstein
🇩🇪Löwenstein, Germany
State Budgetary Institution of Arkhangelsk Oblast "Arkhangelsk Region Clinical Oncology Center
🇷🇺Arkhangelsk, Russian Federation
Military Medical Academy
🇷🇸Belgrade, Serbia
Budgetary Healthcare Institution of Omsk Region "Clinical Oncology Center"
🇷🇺Omsk, Russian Federation
Zaporozhye Regional Clinical Oncology Center
🇺🇦Zaporozhye, Ukraine
OKZ "Sumskyi oblasnyi klinichnyi onkolohichnyi dyspanser"
🇺🇦Sumy, Ukraine
Seoul National University Bundang Hospital
🇰🇷Seongnam, Korea, Republic of
Gangnam Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Klinikum Kassel
🇩🇪Kassel, Germany
State Budgetary Healthcare Institution "Regional Clinical Hospital #1 n.a. professor S.V. Ochapovsky" of Ministry of Healthcare of Krasnodar Region
🇷🇺Krasnodar, Russian Federation
State Budgetary Healthcare Institution of Novosibirsk Region "Novosibirsk Region Clinical Oncology Center"
🇷🇺Novosibirsk, Russian Federation
State Budgetary Healthcare Institution Leningradskaya Region Clinical Hospital
🇷🇺Saint-Petersburg, Russian Federation
Federal State Budgetary Institution " Scientific Research Institute of Oncology n.a. N.N. Petrov" of Ministry of Healthcare of the Russian Federation
🇷🇺Saint-Petersburg, Russian Federation
Csongrád Megyei Önkormányzat Mellkasi Betegségek Szakkó
🇭🇺Deszk, Hungary
Mogilev Regional Oncological Dispensary
🇧🇾Mogilev, Belarus
N. N. Alexandrov Republican Scientific and Practical Center of Oncology and Medical Radiology
🇧🇾Lesnoy, Belarus
New Vision University Hospital
🇬🇪Tbilisi, Georgia
LTD MediClubGeorgia
🇬🇪Tbilisi, Georgia
LTD Chemotherapy and Immunotherapy Clinic Medulla
🇬🇪Tbilisi, Georgia
ICO-Institute of Clinical Oncology
🇬🇪Tbilisi, Georgia
Evangelisches Krankenhaus Bielefeld
🇩🇪Bielefeld, Germany
Universitätsklinikum Bonn
🇩🇪Bonn, Germany
LungenClinic Grosshansdorf GmbH
🇩🇪Grosshansdorf, Germany
University Hospital Homburg
🇩🇪Homburg, Germany
Klinikum der Stadt Ludwigshafen
🇩🇪Ludwigshafen, Germany
Universitätsklinikum Leipzig [Pneumologie]
🇩🇪Leipzig, Germany
Orszagos Koranyi Tbc Es Pulmonologiai Intezet, Iv. Tudobel
🇭🇺Budapest, Hungary
Országos Korányi TBC és Pulmonológiai Intézet
🇭🇺Budapest, Hungary
Inje University Haeundae Paik Hospital
🇰🇷Busan, Korea, Republic of
Veszprem Megyei Onkormanyzat Tudogyogyintezete
🇭🇺Farkasgyepu, Hungary
Markusovszky Egyetemi Oktatókórház
🇭🇺Szombathely, Hungary
Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz - Rendeloint
🇭🇺Szolnok, Hungary
Dong-A University Hospital
🇰🇷Busan, Korea, Republic of
Chonbuk National University Hospital
🇰🇷Jeonju, Korea, Republic of
Gyeongsang National University Hospital
🇰🇷Jinju-si, Korea, Republic of
CHA Bundang Medical Center, CHA University
🇰🇷Seongnam, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Catholic University of Korea, St. Vincent's Hospital
🇰🇷Suwon-si, Korea, Republic of
Oncocenter Oncologie Clinica
🇷🇴Timisoara, Romania
Yonsei Universtiy, Wonju Severance Christian Hospital
🇰🇷Wonju, Korea, Republic of
MED-POLONIA Sp.z o.o.
🇵🇱Poznan, Poland
Mazowieckie Centrum Leczenia Chorob Pluc i Gruzlicy
🇵🇱Otwock, Poland
Samodzielny Publiczny Zespol Gruzlicy i Chorob Pluc
🇵🇱Olsztyn, Poland
Med Life
🇷🇴Bucuresti, Romania
Medisprof
🇷🇴Cluj-Napoca, Romania
Centrul de Oncologie Sf. Nectarie
🇷🇴Craiova, Romania
Centrul de Oncologie Euroclinic
🇷🇴Iasi, Romania
Radiotherapy Center CJ radioterapie si chimioterapie adulti
🇷🇴Floresti, Romania
Oncolab
🇷🇴Craiova, Romania
Institutul Regional de Oncologie Iasi
🇷🇴Iasi, Romania
State Autonomous Healthcare Institution "Republican Clinical Oncology Center of Ministry of Healthcare of Tatarstan Republic"
🇷🇺Kazan, Russian Federation
State Budgetary Healthcare Institution "Chelyabinsk Regional Clinical Oncology Center"
🇷🇺Chelyabinsk, Russian Federation
Federal State Budgetary Scientific Institution " N.N. Blokhin Russian Cancer Research Center" of the Ministry of Health of the Russian Federation
🇷🇺Moscow, Russian Federation
State Autonomous Healthcare Institution of Moscow "Moscow City Oncology Hospital # 62 of Healthcare Department of Moscow"
🇷🇺Moscow, Russian Federation
State Regional Budgetary Healthcare Institution "Murmansk Regional Oncology Center"
🇷🇺Murmansk, Russian Federation
State Budgetary Healthcare Institution of Nizhny Novgorod oblast "Nizhny Novgorod Region Oncology Center"
🇷🇺Nizhniy Novgorod, Russian Federation
Federal Budgetary Healthcare Insittution "Saint-Petersburg Clinical Hospital of RAS"
🇷🇺Saint-Petersburg, Russian Federation
Federal State Budgetary Educational Institution of Higher Education "Academician I.P. Pavlov First St. Petersburg State Medical University" of the Ministry of Healthcare of the Russian Federation./ Scientific Research Institute of Pulmonology
🇷🇺Saint-Petersburg, Russian Federation
State Budgetary Healthcare Institution " Oncology Center #2" of Krasnodar Region Ministry of Healthcare
🇷🇺Sochi, Russian Federation
Private foundation of Educational establishment of Higher Education Medical University "REAVIZ"
🇷🇺Samara, Russian Federation
State Budgetary Healthcare Institution of Yaroslavl Region "Regional Clinical Oncology Hospital"
🇷🇺Yaroslavl, Russian Federation
State Budgetary Healthcare Institution "Volgograd Regional Clinical Oncology Center"
🇷🇺Volzhskiy, Russian Federation
Saint-Petersburg State Budgetary Healthcare Institution "City Clinical Oncology Center"
🇷🇺Saint-Petersburg, Russian Federation
State Budgetary Healthcare Institution Republican Clinical Oncology Center of Ministry of Healthcare of the Republic of Bashkortostan
🇷🇺Ufa, Russian Federation
H.U. Severo Ochoa
🇪🇸Leganés, Spain
State Budgetary Healthcare Institution of Sverdlovskaya Oblast "Sverdlovsk Regional Oncology Center"
🇷🇺Yekaterinburg, Russian Federation
Clinical Hospital Center Bezanijska Kosa
🇷🇸Belgrade, Serbia
Clinical Center Kragujevac, Clinic for Pulmology
🇷🇸Kragujevac, Serbia
Clinical Centre Nis
🇷🇸Nis, Serbia
H.G.U. G. Marañón
🇪🇸Madrid, Spain
C.H. Provincial de Castellón
🇪🇸Castelló de la Plana, Spain
H.U. F. Jiménez Díaz
🇪🇸Madrid, Spain
C.H.U. de Canarias
🇪🇸Santa Cruz de Tenerife, Spain
H.U.N. Sra. Valme
🇪🇸Sevilla, Spain
C.H. de Orense
🇪🇸Ourense, Spain
H.U. Sant Joan de Reus
🇪🇸Reus, Spain
Clínica Universidad de Navarra
🇪🇸Pamplona, Spain
Changhua Christian Hospital
🇨🇳Changhua, Taiwan
Siriraj Hospital
🇹🇭Bangkok, Thailand
China Medical University Hospital
🇨🇳Taichung, Taiwan
ChiangMai Univerisity
🇹🇭Chiang Mai, Thailand
Chiangrai Prachanukroh Hospital
🇹🇭Chiang Rai, Thailand
Prince of Songkla University
🇹🇭Hat Yai, Thailand
Komunalna ustanova "Chernivetskyi oblasnyi klinichnyi onkolo
🇺🇦Chernivtsi, Ukraine
Kharkivskyi oblasnyi onkologichnyi klinichnyi tsentr
🇺🇦Kharkiv, Ukraine
Komunalnyi zaklad Miska bahatoprofilna klinichna likarnia #4
🇺🇦Dnipropetrovsk, Ukraine
Odeskyi oblasnyi onkolohichnyi dyspanser
🇺🇦Odesa, Ukraine
Vinnytskyi oblasnyi klinichnyi onkolohichnyi dyspanser
🇺🇦Vinnytsia, Ukraine
Khmelnytskyi oblasnyi onkolohichnyi dyspanser
🇺🇦Khmelnytskyi, Ukraine
JSC Maritime Hospital
🇬🇪Batumi, Georgia
Institute for Personalized Medicine LTD
🇬🇪Tbilisi, Georgia
Pelican Impex
🇷🇴Oradea, Romania
Vitebsk Regional Clinical Oncological Dispensary
🇧🇾Vitebsk, Belarus
JSC Saint Nikolozi Surgery Center
🇬🇪Kutaisi, Georgia
Spitalul Universitar de Urgenta Bucuresti
🇷🇴Bucuresti, Romania
Udonthani Cancer Hospital
🇹🇭Udon Thani, Thailand
Spitalul Clinic Judetean de Urgenta Constanta
🇷🇴Constanta, Romania
Chang Gung Medical Foundation, Linkou
🇨🇳Taoyuan, Taiwan
Kaohsiung Medical University Chung-Ho Memorial Hospital
🇨🇳Kaohsiung, Taiwan