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

December 11, 2024 updated by: Samsung Bioepis Co., Ltd.

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

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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

Study Type

Interventional

Enrollment (Actual)

763

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belarus
      • Brest, Belarus, 224027
        • Brest Regional Oncology Dispensary
      • Grodno, Belarus, 230017
        • Grodno Regional Clinical Hospital
      • Lesnoy, Belarus, 223040
        • N. N. Alexandrov Republican Scientific and Practical Center of Oncology and Medical Radiology
      • Minsk, Belarus, 220013
        • Minsk city Clinical Oncological Dispensary
      • Mogilev, Belarus, 212018
        • Mogilev Regional Oncological Dispensary
      • Vitebsk, Belarus, 210603
        • Vitebsk Regional Clinical Oncological Dispensary
  • Georgia
      • Batumi, Georgia, 6010
        • JSC Maritime Hospital
      • Kutaisi, Georgia, 4600
        • JSC Saint Nikolozi Surgery Center
      • Tbilisi, Georgia, 0112
        • LTD Research Institute of Clinical Medicine
      • Tbilisi, Georgia, 0160
        • LTD MediClubGeorgia
      • Tbilisi, Georgia, 0159
        • ICO-Institute of Clinical Oncology
      • Tbilisi, Georgia, 0159
        • New Vision University Hospital
      • Tbilisi, Georgia, 0186
        • Institute for Personalized Medicine LTD
      • Tbilisi, Georgia, 0186
        • LTD Chemotherapy and Immunotherapy Clinic Medulla
  • Germany
      • Bielefeld, Germany, 33611
        • Evangelisches Krankenhaus Bielefeld
      • Bonn, Germany, 53127
        • Universitatsklinikum Bonn
      • Grosshansdorf, Germany, 22927
        • LungenClinic Grosshansdorf GmbH
      • Homburg, Germany, 66421
        • University Hospital Homburg
      • Kassel, Germany, 34125
        • Klinikum Kassel
      • Leipzig, Germany, 04103
        • Universitätsklinikum Leipzig [Pneumologie]
      • Ludwigshafen, Germany, 67063
        • Klinikum der Stadt Ludwigshafen
      • Löwenstein, Germany, 74245
        • Klinik Löwenstein
  • Hungary
      • Budapest, Hungary, 1121
        • Orszagos Koranyi Tbc es Pulmonologiai Intezet
      • Budapest, Hungary, 1521
        • Orszagos Koranyi Tbc es Pulmonologiai Intezet
      • Budapest, Hungary, H-1529
        • Orszagos Koranyi Tbc Es Pulmonologiai Intezet, Iv. Tudobel
      • Deszk, Hungary, 6772
        • Csongrád Megyei Önkormányzat Mellkasi Betegségek Szakkó
      • Farkasgyepu, Hungary, 8582
        • Veszprem Megyei Onkormanyzat Tudogyogyintezete
      • Szolnok, Hungary, 5004
        • Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz - Rendeloint
      • Szombathely, Hungary, H-9700
        • Markusovszky Egyetemi Oktatokorhaz
  • Korea, Republic of
      • Busan, Korea, Republic of, 48108
        • Inje University Haeundae Paik Hospital
      • Busan, Korea, Republic of, 49201
        • Dong-A University Hospital
      • Jeonju, Korea, Republic of, 561-712
        • Chonbuk National University Hospital
      • Jinju-si, Korea, Republic of, 52727
        • Gyeongsang National University Hospital
      • Seongnam, Korea, Republic of, 13620
        • Seoul National University Bundang Hospital
      • Seongnam, Korea, Republic of, 13496
        • CHA Bundang Medical Center, CHA University
      • Seoul, Korea, Republic of, 135-710
        • Samsung Medical Center
      • Seoul, Korea, Republic of, 06273
        • Gangnam Severance Hospital, Yonsei University Health System
      • Suwon-si, Korea, Republic of, 442-723
        • Catholic University of Korea, St. Vincent's Hospital
      • Wonju, Korea, Republic of, 26426
        • Yonsei Universtiy, Wonju Severance Christian Hospital
  • Poland
      • Olsztyn, Poland, 10-357
        • Samodzielny Publiczny Zespol Gruzlicy i Chorob Pluc
      • Otwock, Poland, 05-400
        • Mazowieckie Centrum Leczenia Chorob Pluc I Gruzlicy
      • Poznan, Poland, 60-693
        • MED-POLONIA Sp.z o.o.
  • Romania
      • Bucuresti, Romania, 050098
        • Spitalul Universitar de Urgenta Bucuresti
      • Bucuresti, Romania, 031784
        • Med Life
      • Cluj-Napoca, Romania, 400058
        • Medisprof
      • Constanta, Romania, 900591
        • Spitalul Clinic Judetean de Urgenta Constanta
      • Craiova, Romania, 200347
        • Centrul de Oncologie Sf. Nectarie
      • Craiova, Romania, 200385
        • Oncolab
      • Floresti, Romania, 407280
        • Radiotherapy Center CJ radioterapie si chimioterapie adulti
      • Iasi, Romania, 700106
        • Centrul de Oncologie Euroclinic
      • Iasi, Romania, 700483
        • Institutul Regional de Oncologie Iasi
      • Oradea, Romania, 410469
        • Pelican Impex
      • Timisoara, Romania, 300210
        • Oncocenter Oncologie Clinica
  • Russian Federation
      • Arkhangelsk, Russian Federation, 163045
        • State Budgetary Institution of Arkhangelsk Oblast "Arkhangelsk Region Clinical Oncology Center
      • Chelyabinsk, Russian Federation, 454087
        • State Budgetary Healthcare Institution "Chelyabinsk Regional Clinical Oncology Center"
      • Kazan, Russian Federation, 420029
        • State Autonomous Healthcare Institution "Republican Clinical Oncology Center of Ministry of Healthcare of Tatarstan Republic"
      • Krasnodar, Russian Federation, 350086
        • State Budgetary Healthcare Institution "Regional Clinical Hospital #1 n.a. professor S.V. Ochapovsky" of Ministry of Healthcare of Krasnodar Region
      • Moscow, Russian Federation, 115478
        • Federal State Budgetary Scientific Institution " N.N. Blokhin Russian Cancer Research Center" of the Ministry of Health of the Russian Federation
      • Moscow, Russian Federation, 143423
        • State Autonomous Healthcare Institution of Moscow "Moscow City Oncology Hospital # 62 of Healthcare Department of Moscow"
      • Murmansk, Russian Federation, 183047
        • State Regional Budgetary Healthcare Institution "Murmansk Regional Oncology Center"
      • Nizhniy Novgorod, Russian Federation, 603081
        • State Budgetary Healthcare Institution of Nizhny Novgorod oblast "Nizhny Novgorod Region Oncology Center"
      • Novosibirsk, Russian Federation, 630108
        • State Budgetary Healthcare Institution of Novosibirsk Region "Novosibirsk Region Clinical Oncology Center"
      • Omsk, Russian Federation, 644013
        • Budgetary Healthcare Institution of Omsk Region "Clinical Oncology Center"
      • Saint-Petersburg, Russian Federation, 194017
        • Federal Budgetary Healthcare Insittution "Saint-Petersburg Clinical Hospital of RAS"
      • Saint-Petersburg, Russian Federation, 194291
        • State Budgetary Healthcare Institution Leningradskaya Region Clinical Hospital
      • Saint-Petersburg, Russian Federation, 197022
        • 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, 197758
        • 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, 198255
        • Saint-Petersburg State Budgetary Healthcare Institution "City Clinical Oncology Center"
      • Samara, Russian Federation, 443011
        • Private foundation of Educational establishment of Higher Education Medical University "REAVIZ"
      • Sochi, Russian Federation, 354057
        • State Budgetary Healthcare Institution " Oncology Center #2" of Krasnodar Region Ministry of Healthcare
      • Ufa, Russian Federation, 450054
        • State Budgetary Healthcare Institution Republican Clinical Oncology Center of Ministry of Healthcare of the Republic of Bashkortostan
      • Volzhskiy, Russian Federation, 404130
        • State Budgetary Healthcare Institution "Volgograd Regional Clinical Oncology Center"
      • Yaroslavl, Russian Federation, 150040
        • State Budgetary Healthcare Institution of Yaroslavl Region "Regional Clinical Oncology Hospital"
      • Yekaterinburg, Russian Federation, 620036
        • State Budgetary Healthcare Institution of Sverdlovskaya Oblast "Sverdlovsk Regional Oncology Center"
  • Serbia
      • Belgrade, Serbia, 11000
        • Military Medical Academy
      • Belgrade, Serbia, 11070
        • Clinical Hospital Center Bezanijska Kosa
      • Kragujevac, Serbia, 34000
        • Clinical Center Kragujevac, Clinic for Pulmology
      • Nis, Serbia, 18000
        • Clinical Centre Nis
  • Spain
      • Castelló de la Plana, Spain, 12002
        • C.H. Provincial de Castellón
      • Leganés, Spain, 28911
        • H.U. Severo Ochoa
      • Madrid, Spain, 28007
        • H.G.U. G. Marañón
      • Madrid, Spain, 28040
        • H.U. F. Jiménez Díaz
      • Ourense, Spain, 32005
        • C.H. de Orense
      • Pamplona, Spain, 31008
        • Clinica Universidad de Navarra
      • Reus, Spain, 43204
        • H.U. Sant Joan de Reus
      • Santa Cruz de Tenerife, Spain, 38320
        • C.H.U. de Canarias
      • Sevilla, Spain, 41014
        • H.U.N. Sra. Valme
  • Taiwan
      • Changhua, Taiwan, 50006
        • Changhua Christian Hospital
      • Kaohsiung, Taiwan, 807
        • Kaohsiung Medical University Chung-Ho Memorial Hospital
      • Kaohsiung, Taiwan, 824
        • E-Da Hospital
      • Taichung, Taiwan, 40447
        • China Medical University Hospital
      • Taoyuan, Taiwan, 33305
        • Chang Gung Medical Foundation, Linkou
  • Thailand
      • Bangkok, Thailand, 10700
        • Siriraj Hospital
      • Chiang Mai, Thailand, 50200
        • ChiangMai Univerisity
      • Chiang Rai, Thailand, 57000
        • Chiangrai Prachanukroh Hospital
      • Hat Yai, Thailand, 90110
        • Prince of Songkla University
      • Udon Thani, Thailand, 41330
        • Udonthani Cancer Hospital
  • Ukraine
      • Chernivtsi, Ukraine, 58013
        • Komunalna ustanova "Chernivetskyi oblasnyi klinichnyi onkolo
      • Dnipropetrovsk, Ukraine, 49102
        • Komunalnyi zaklad Miska bahatoprofilna klinichna likarnia #4
      • Kharkiv, Ukraine, 61070
        • Kharkivskyi oblasnyi onkologichnyi klinichnyi tsentr
      • Khmelnytskyi, Ukraine, 29009
        • Khmelnytskyi oblasnyi onkolohichnyi dyspanser
      • Odesa, Ukraine, 65055
        • Odeskyi oblasnyi onkolohichnyi dyspanser
      • Sumy, Ukraine, 40022
        • OKZ "Sumskyi oblasnyi klinichnyi onkolohichnyi dyspanser"
      • Vinnytsia, Ukraine, 21029
        • Vinnytskyi oblasnyi klinichnyi onkolohichnyi dyspanser
      • Zaporozhye, Ukraine, 69040
        • Zaporozhye Regional Clinical Oncology Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Aged ≥ 18 years
  2. ECOG performance status of 0-1
  3. Histologically-confirmed metastatic or recurrent non-squamous non-small cell lung cancer
  4. At least one measurable lesion according to RECIST v1.1.
  5. Able to receive bevacizumab, carboplatin and paclitaxel based on adequate laboratory and clinical parameters

Exclusion Criteria:

  1. Diagnosis of small cell carcinoma of the lung or squamous cell carcinoma
  2. Sensitizing EGFR mutations or ALK rearrangements
  3. Increased risk of bleeding determined by investigator based on radiographic / clinical findings
  4. History of systemic chemotherapy administered in the first-line setting for metastatic or recurrent disease of NSCLC.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Best Overall Response (Best Overall Response Rate[ORR]) by 24 Weeks
Time Frame: 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.
24 weeks from randomisation

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression Free Survival
Time Frame: 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).
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
Time Frame: 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.
from the date of randomisation to the date of death up to 12 months from randomisation of the last subject
Duration of Response (DoR)
Time Frame: 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
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
Time Frame: 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 AE
AEs were reported from the time the informed consent form (ICF) was signed until the EOT visit, approximately 24 months from study initiation.
Pharmacokinetics: Trough Level [Ctrough]
Time Frame: 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)
Up to 21 weeks (Cycle 1,3,5 and 7. Each cycle is 21 days.)
Pharmacokinetics: Maximum Plasma Concentration [Cmax]
Time Frame: 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)
Up to 21 weeks (Cycle 1,3,5 and 7. Each cycle is 21 days.)
Immunogenicity Assessments (Anti-drug Antibodies)
Time Frame: 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.
Up to 21 weeks (Cycle 1,3,5, 7 and EOT visit. Each cycle is 21 days.), approximately 24 months from study initiation.
Immunogenicity Assessments (Neutralizing Antibodies)
Time Frame: 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).
Up to 21 weeks (Cycle 1,3,5, 7 and EOT visit. Each cycle is 21 days.), approximately 24 months from study initiation.

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Best Objective Response Rate by 11 and 17 Weeks
Time Frame: 11 weeks and 17 weeks from randomisation
Best Objective Response Rate (ORR) by 11 weeks and 17 weeks
11 weeks and 17 weeks from randomisation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Samsung Bioepis Co., Ltd.

Investigators

  • Principal Investigator: Martin Reck, M.D., LungenClinic Grosshansdorf, Germany

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 5, 2016

Primary Completion (Actual)

January 24, 2018

Study Completion (Actual)

October 9, 2018

Study Registration Dates

First Submitted

March 24, 2016

First Submitted That Met QC Criteria

April 25, 2016

First Posted (Estimated)

April 28, 2016

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

December 11, 2024

Last Verified

December 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SB8-G31-NSCLC

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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