A Study Comparing MB02 and Avastin® in Subjects With Stage IIIB/IV Non-Squamous Non-Small Cell Lung Cancer (NSCLC)

NCT ID: NCT03296163

Last Updated: 2021-04-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 627 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-02-06
• Study Completion Date: 2020-02-27

Brief Summary

This is a multicenter, multinational, double-blind, 1:1 randomized, parallel-group, equivalence Phase 3 study to compare the efficacy and safety of MB02 plus chemotherapy (carboplatin and paclitaxel) versus Avastin® plus chemotherapy (carboplatin and paclitaxel) in subjects with Stage IIIB/IV non-squamous NSCLC

Detailed Description

Efficacy parameters, safety profiles and immunogenicity will be compared between MB02 (Bevacizumab Biosimilar Drug) and European (EU)-approved Avastin®

Conditions

Non-small Cell Lung Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

MB02 (Bevacizumab Biosimilar Drug)

MB02 (Bevacizumab Biosimilar Drug) + Carboplatin/Paclitaxel

Group Type: EXPERIMENTAL

MB02 (Bevacizumab Biosimilar Drug)

Intervention Type: DRUG

15 mg/kg IV every 3 weeks on Day 1

Carboplatin

Intervention Type: DRUG

Carboplatin Area under the curve (AUC) 6 IV every 3 weeks on Day 1 for 6 cycles

Paclitaxel

Intervention Type: DRUG

Paclitaxel 200 mg/m2 IV every 3 weeks on Day 1 for 6 cycles

EU-approved Avastin®

EU-approved Avastin® + Carboplatin/Paclitaxel

Group Type: ACTIVE_COMPARATOR

EU-approved Avastin®

Intervention Type: DRUG

15 mg/kg IV every 3 weeks on Day 1

Carboplatin

Intervention Type: DRUG

Carboplatin Area under the curve (AUC) 6 IV every 3 weeks on Day 1 for 6 cycles

Paclitaxel

Intervention Type: DRUG

Paclitaxel 200 mg/m2 IV every 3 weeks on Day 1 for 6 cycles

Interventions

MB02 (Bevacizumab Biosimilar Drug)

15 mg/kg IV every 3 weeks on Day 1

Intervention Type: DRUG

EU-approved Avastin®

15 mg/kg IV every 3 weeks on Day 1

Intervention Type: DRUG

Carboplatin

Carboplatin Area under the curve (AUC) 6 IV every 3 weeks on Day 1 for 6 cycles

Intervention Type: DRUG

Paclitaxel

Paclitaxel 200 mg/m2 IV every 3 weeks on Day 1 for 6 cycles

Intervention Type: DRUG

Other Intervention Names

Bevacizumab; Bevacizumab; Taxol

Eligibility Criteria

Inclusion Criteria

1. Males and female subjects aged ≤ 18 years to ≤ 80 years.

2. Signed informed consent must be obtained before initiation of any study-specific procedures or treatment as confirmation of the subject's awareness and willingness to comply with the study requirements.

Exclusion Criteria

4. Previous radiation therapy if completed >4 weeks before randomization. Palliative radiotherapy to bone lesions is allowed if completed >2 weeks of randomization.

5. Subjects must have at least 1 unidimensional measurable lesion per RECIST version 1.1 (assessed locally).

6. Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status ≤1 at Screening.

7. Subjects must have adequate hepatic, renal and hematologic function defined as:

• Hepatic function: bilirubin level <1.5 the upper limit of normal (ULN), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels<2.5×ULN.
• Renal function: serum creatinine level <1.5×ULN, calculated creatinine clearance (CrCl) >50 mL/min (Cockcroft-Gault formula), urine protein to creatinine ratio <1. Subjects with urine protein-to-creatinine ratio >1 may be enrolled if they have <1 g of protein in 24-hour urine collection.
• Hematological function: Absolute neutrophil count >1.5×109 /L; platelets >100×109 /L, hemoglobin (Hb) >9 g/dL.
• Adequate coagulation parameters such as: INR ≤ 2.0 and aPTT ≤ 1.5 x ULN within 7 days prior to randomization for patients not receiving anticoagulation therapy.

8. Eligible subjects must have a systolic blood pressure of ≤ 140 mm Hg and a diastolic blood pressure of ≤90 mm Hg at screening.

9. Women of childbearing potential, and their partners, must agree to adhere to pregnancy prevention methods throughout the duration of the study (including the Follow-up visits, where applicable). Women of childbearing potential are defined as those who are not surgically sterile (did not underwent bilateral tubal ligation, bilateral oophorectomy, or hysterectomy) and not postmenopausal.

Subjects and their partners must agree to use a highly effective method of contraception, to avoid women becoming pregnant throughout the course of the study. Medically acceptable forms of birth control can include the following, with approval of the treating physician:

• Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, or transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomized partner, sexual abstinence.

10. Non fertile women can be included, that is, those who are physiologically incapable of becoming pregnant, because of:

• Hysterectomy.
• Bilateral oophorectomy (ovariectomy).
• Bilateral tubal ligation or,
• Postmenopausal women defined as:

Subjects not using hormone replacement therapy (HRT) and have experienced total cessation of menses for ≥ 1 year and be greater than 45 years of age, OR, in questionable cases, have a follicle stimulating hormone >40 mIU/mL and an estradiol value <40 pg/mL (<140 pmol/L).

Subjects must discontinue HRT before study enrolment because of the potential for inhibition of cytochrome enzymes that metabolize estrogens and progestins. For most forms of HRT, at least 2 to 4 weeks must elapse between the cessation of HRT and determination of menopausal status; the length of this interval depends on the type and dosage of HRT.

If a female subject is determined not to be postmenopausal, that subject must use adequate contraception, as defined immediately above (inclusion 8).

1. Inability to comply with protocol procedures.

2. Participation in another clinical trial or treatment with another investigational agent within 4 weeks or 5 half-lives of investigational agent before randomization, whichever is longer.

3. Subjects previously treated with monoclonal antibodies or small molecule inhibitors against Vascular Endothelial Growth Factor (VEGF) or VEGF receptors, including Avastin®.

4. Subjects who have received previous chemotherapy, immunotherapy, targeted therapy, or biological therapy for their lung cancer. Note: Adjuvant and neo- adjuvant therapy are permitted (see: inclusion criterion 3).

5. Subjects who have known central nervous system disease, with the exception of subjects with treated brain metastases who have completed treatment (radiation, surgery or stereotactic surgery) and have not received steroids for at least 4 weeks before randomization. Subjects with central nervous system metastases treated by neurosurgical resection or brain biopsy performed within 8 weeks before randomization will be excluded. Subjects with known or history of brain metastases must undergo brain imaging during screening.

6. Current or recent (within 10 days of the first dose of study treatment) use of aspirin (at least 325 mg/day) or other nonsteroidal anti-inflammatory drugs with antiplatelet activity or treatment with dipyridamole (Persantine®), ticlopidine (Ticlid®), clopidogrel (Plavix®), or cilostazol (Pletal®).

7. Current or recent (within 5 days) use of therapeutic anticoagulation or use of thrombolytic agent. Prophylactic use of low molecular weight heparin is allowed.

8. Subjects with an INR >2, unless receiving active anticoagulation treatment, will be excluded.

9. Subjects who have a diagnosis of small cell carcinoma of the lung or squamous cell carcinoma of the lung. Mixed tumors should be categorized according to the predominant histology. If small cell elements are present, the subject will be excluded.

10. Subjects with known tumors that harbor activating epidermal growth factor receptor and anaplastic lymphoma receptor tyrosine kinase (assessed locally).

11. Subjects who have a history of hypersensitivity to the active substance (bevacizumab, carboplatin, and/or paclitaxel) or any of the excipients (such as trehalose dehydrate, sodium phosphate, or polysorbate 20).

12. Subjects with known active viral infection, including but not limited to: hepatitis B, hepatitis C, or HIV.

13. Subjects who are pregnant or breastfeeding. Women of child-bearing potential must have a negative pregnancy test at Screening.

14. Subjects with previous major surgery, open biopsy, open pleurodesis, or significant traumatic injury within 4 weeks before randomization or those anticipated to require major surgery during the study.

15. Subjects who have had a core biopsy taken or have had another minor surgical procedure, excluding placement of vascular access device, closed pleurodesis, thoracentesis, and mediastinoscopy, within 1 week of randomization.

16. Subjects with a history of abdominal fistula, GI perforation, intra-abdominal abscess within 6 months of randomization.

17. Subjects with a nonhealing wound, active ulcer, or untreated bone fracture.

18. Subjects with previous history of hypertensive crisis or hypertensive encephalopathy.

19. Subjects with New York Heart Association Grade II or greater congestive heart failure, or angina, myocardial infarction within 6 months before randomization; symptomatic arrhythmia or serious cardiac arrhythmia requiring medication; abnormal left ventricular ejection fraction < 50% assessed by ultrasound or multigated acquisition scan.

20. Subjects with a previous malignancy within 3 years of randomization (other than superficial basal cell and superficial squamous (skin) cell carcinoma, or carcinoma in situ of the uterine cervix, bladder, or prostate).

21. Subjects with history of a significant vascular event within 6 months before randomization (including, but not limited to myocardial infarction and stroke or transient ischemic attack).

22. Subjects with known bleeding diathesis or significant coagulopathy defined as a bleeding event grade ≥ 2 within 3 months before randomization.

23. Subjects with history of grade ≥2 hemoptysis within 6 months before randomization (≥0.5 teaspoons of bright red blood per event).

24. Subjects with a tumor(s) invading or compressing major blood vessels.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

mAbxience Research S.L.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

MedRadius

Maceió, Alagoas, Brazil

Instituto do Câncer do Ceará - ICC

Fortaleza, Ceará, Brazil

Centro Brasileiro de Radioterapia Oncologia e Mastologia

Goiânia, Goiás, Brazil

Hospital Erasto Gaertner - Paranaense de Combate ao Câncer

Curitiba, Paraná, Brazil

Instituto Nacional de Cancer- INCA

Rio de Janeiro, Rio de Janeiro, Brazil

Centro de Pesquisa e Educação da Serra Gaúcha (CEPESG)

Caxias do Sul, Rio Grande do Sul, Brazil

IPCEM Universidade de Caxias Do Sul

Caxias do Sul, Rio Grande do Sul, Brazil

Hospital de Caridade de Ijuí

Ijuí, Rio Grande do Sul, Brazil

Instituto do Câncer - Hospital São Vicente de Paulo

Passo Fundo, Rio Grande do Sul, Brazil

Hospital São Lucas da PUCRS

Pôrto Alegre, Rio Grande do Sul, Brazil

Hospital de Câncer de Barretos

Barretos, São Paulo, Brazil

Hospital de Base de São José do Rio Preto

São José Do Rio Prêto, São Paulo, Brazil

Centro de Pesquisa do Instituto Brasileiro de Controle do Câncer - IBCC

São Paulo, São Paulo, Brazil

Instituto de Ensino e Pesquisa São Lucas

São Paulo, São Paulo, Brazil

Hospital Santa Marcelina

São Paulo, , Brazil

Central Hospital Plovdiv

Plovdiv, , Bulgaria

Acıbadem City Clinic Cancer Center UMHAT

Sofia, , Bulgaria

Specialized Hospital for Active Treatment of Oncology Diseases Sofia District EOOD

Sofia, , Bulgaria

Fundación Arturo López Pérez - Instituto Oncológico FALP

Santiago, , Chile

Health & Care Spa

Santiago, , Chile

Instituto Clinico Oncologico del Sur ICOS

Temuco, , Chile

Oncocentro APYS

Viña del Mar, , Chile

Cancer Center of Adjara Autonomous Republic

Batumi, , Georgia

Acad. F . Todua medical center-research institute of clinical medicine

Tbilisi, , Georgia

Consilium Medulla

Tbilisi, , Georgia

Institute of Clinical Oncology

Tbilisi, , Georgia

LTD Aversi Clinic

Tbilisi, , Georgia

LTD Cancer Research Centre

Tbilisi, , Georgia

Tbilisi State Medical Universitys First university Clinic

Tbilisi, , Georgia

General Hospital of Athens "Ippokratio"

Athens, , Greece

Sotiria General Hospital for Chest Diseases

Athens, , Greece

University General Hospital of Larissa

Larissa, , Greece

Agioi Anargyroi General Oncological Hospital of Kifissia

Nea Kifissia, , Greece

General Hospital of Thessaloniki "George Papanikolaou"

Thessaloniki, , Greece

National Koranyi Institute of TB and Pulmonology

Budapest, , Hungary

Országos Korányi Pulmonológiai Intézet (OKPI)

Budapest, , Hungary

Csongrád Megyei Önkormányzat Mellkasi Betegségek Szakkórháza

Deszk, , Hungary

Veszprém Megyei Tüdőgyógyinzézet

Farkasgyepű, , Hungary

Borsod-Abaúj-Zemplén Megyei Központi Kórház és Egyetemi Oktatókórház

Miskolc, , Hungary

Zydus Hospital

Ahmedabad, , India

Action Cancer Hospital

Delhi, , India

Aadhar Health Institute

Hisar, , India

NIMS - Nizam's Institute of Medical Sciences

Hyderabad, , India

Ganadhipati Purushottam Shekhawati Hospital Research Centre

Jaipur, , India

PVS Hospital Pvt Ltd

Kerola, , India

Apollo Gleneagles Hospital

Kolkata, , India

Netaji Subhas Chandra Bose Cancer Research Institute

Kolkata, , India

Shatabdi Super Speciality Hospital

Nashik, , India

Deenanath Mangeshkar Hospital & Research Center

Pune, , India

Nirmal Hospital Pvt. Ltd.

Surat, , India

Kiran Super Multispeciality Hospital

Sūrat, , India

Shree Himalaya Cancer Hospital Research Institute

Vadodara, , India

Queen's NRI Hospital Gurudwara Lane

Visakhapatnam, , India

Notre Dame de Secours

Byblos, , Lebanon

Hospital Pulau Pinang

George Town, Pulau Pinang, Malaysia

Institut Perubatan dan Pergigian Termaju Universiti Sains Malaysia

Kepala Batas, , Malaysia

Hospital Kuala Lumpur

Kuala Lumpur, , Malaysia

Pusat Perubatan Universiti Kebangsaan Malaysia

Kuala Lumpur, , Malaysia

University Malaya Medical Centre

Kuala Lumpur, , Malaysia

Hospital Umum Sarawak

Kuching, , Malaysia

National Cancer Institute

Putrajaya, , Malaysia

Instituto Nacional de Cancerologia

Mexico City, , Mexico

Hospital Universitario Dr. Jose Eleuterio González

Monterrey, , Mexico

Sultan Qaboos University Hospital

Muscat, , Oman

Baguio General Hospital & Medical Center

Baguio City, , Philippines

Cebu Doctors University Hospital - CDUH

Cebu, , Philippines

Perpetual Succour Hospital - PSH

Cebu, , Philippines

St. Luke's Medical Center - Global City

City of Taguig, , Philippines

De La Salle University Medical Center - DLSUMC

Dasmariñas, , Philippines

Davao Doctors Hospital - DDH

Davao City, , Philippines

Makati Medical Center

Makati City, , Philippines

Philippine General Hospital - PGH

Manila, , Philippines

The Medical City

Pasig, , Philippines

SBHI Arkhangelsk Region - Arkhangelsk Clinical Oncological Dispensary

Arkhangelsk, , Russia

Regional state budgetary Healthcare Institution "Belgorod oncology dispensary"

Belgorod, , Russia

State Budget Healthcare Institution Ivanovo Regional Oncology Dispensary

Ivanovo, , Russia

Kaluga Regional Clinical Oncology center

Kaluga, , Russia

Republic Clinical Oncology Dispensary

Kazan', , Russia

Kursk Republican Clinical Oncology Dispensary

Kursk, , Russia

"VitaMed" LLC

Moscow, , Russia

Moscow City Oncology Hospital No 62

Moscow, , Russia

N. N. Blokhin Russian Cancer Research Center

Moscow, , Russia

University Headache Clinic LLC

Moscow, , Russia

GBUZ of SK Pyatigorsk Oncology Dispensary

Pyatigorsk, , Russia

Ryazan Regional Clinical Oncology Dispensary

Ryazan, , Russia

City Clinical Oncology Dispensary

Saint Petersburg, , Russia

GUZ "Leningrad Regional Clinical Hospital"

Saint Petersburg, , Russia

State Budgetary healthcare Institution "Samara regional clinical oncology dispensary"

Samara, , Russia

Federal budget Healthcare Institution "Volga District Medical Centre" under Federal Medical and Biological Agency

Veliky Novgorod, , Russia

CHC Bezanijska Kosa

Belgrade, , Serbia

Institute of Oncology and Radiology of Serbia (IORS)

Belgrade, , Serbia

Institute for Pulmonary Diseases of Vojvodina

Kamenitz, , Serbia

Clinical Center Kragujevac

Kragujevac, , Serbia

Clinical center Nis (Clinic for pulmonary diseases)

Niš, , Serbia

Hospital Universitario Puerta de Hierro Majadahonda

Madrid, , Spain

Bangkok International Hospital And Wattanosod Hospital

Bangkok, , Thailand

Chiang Mai University (CMU) - Maharaj Nakhon Chiang Mai Hospital Nakorn Chiang Mai Hospital

Chiang Mai, , Thailand

Chiang Rai Prachanukroh Hospital

Chiang Rai, , Thailand

Songklanagarind Hospital

Hat Yai, , Thailand

Buddhachinaraj Hospital

Phitsanulok, , Thailand

Istanbul Medeniyet University Medical Faculty

Istanbul, , Turkey (Türkiye)

Suat Seren Chest Diseases Hospital

Izmir, , Turkey (Türkiye)

Municipal Institution Cherkasy Regional Oncology Dispensary of Cherkasy Regional Council

Cherkasy, , Ukraine

Public Higher Education Insititution of Ukraine "Bukovinian State Medical University"

Chernivtsi, , Ukraine

Clinical Oncology Dispensary

Dnipro, , Ukraine

Multifield Clinical Hospital No.4

Dnipro, , Ukraine

State Institution "Grigoriev Institute for Medical Radiology National Academy of Medical Science of Ukraine"

Kharkiv, , Ukraine

State Institution "V.T. Zaycev Institute of general and urgent surgery of National academy medical sciences of Ukraine"

Kharkiv, , Ukraine

Medical and Diagnostic Centre Private Enterprise of Private Manufacturing Company "ACINUS"

Kropyvnytskyi, , Ukraine

Municipal Institution "Kryviy Rih Oncology Dispensary" of Dnipropetrovsk Regional Council

Kryvyi Rih, , Ukraine

National Cancer Institute

Kyiv, , Ukraine

National Institute of Cancer

Kyiv, , Ukraine

Healthcare facility "Volyn regional Oncological Dispensary"

Lutsk, , Ukraine

Lviv State Oncology Regional Treatment and Diagnostic Center

Lviv, , Ukraine

Odessa Regional Clinical Oncology Dispensary

Odesa, , Ukraine

Uzhgorod National University

Uzhhorod, , Ukraine

Vinnytsia Regional Clinical Oncology Dispensary

Vinnytsia, , Ukraine

Communal Institution "Zaporizhzhya Regional Clinical Oncological Dispensary" of Zaporizhzhya regional council

Zaporizhzhya, , Ukraine

Countries

Brazil; Bulgaria; Chile; Georgia; Greece; Hungary; India; Lebanon; Malaysia; Mexico; Oman; Philippines; Russia; Serbia; Spain; Thailand; Turkey (Türkiye); Ukraine

References

Trukhin D, Poddubskaya E, Andric Z, Makharadze T, Bellala RS, Charoentum C, Yanez Ruiz EP, Fulop A, Hyder Ali IA, Syrigos K, Katgi N, Lopez Chuken YA, Rumyana I, Reyes-Igama J, Costamilan RC, Del Campo Garcia A, Florez A, Paravisini A, Millan S; STELLA Investigators. Efficacy, Safety and Immunogenicity of MB02 (Bevacizumab Biosimilar) versus Reference Bevacizumab in Advanced Non-Small Cell Lung Cancer: A Randomized, Double-Blind, Phase III Study (STELLA). BioDrugs. 2021 Jul;35(4):429-444. doi: 10.1007/s40259-021-00483-w. Epub 2021 Apr 29.

Reference Type: DERIVED

PMID: 33914256 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

MB02-C-02-17

Identifier Type: -

Identifier Source: org_study_id