STELLA – A Randomized, Multicenter, Multinational, Double-Blind Study to Assess the Efficacy and Safety of MB02 (Bevacizumab Biosimilar Drug) Versus Avastin® in Combination With Carboplatin and Paclitaxel for the Treatment of Subjects With Stage IIIB/IV Non-squamous Non-Small Cell Lung Cancer (NSCLC)

• Register: EUCTR
• Last refreshed on: 5 April 2021
• Main ID: EUCTR2017-001769-26-BG
• Date of registration: 10/11/2017
• Prospective Registration: Yes
• Primary sponsor: mAbxience Research SL
• Public title: STELLA – A Randomized, Multicenter, Multinational, Double-Blind Study to Assess the Efficacy and Safety of MB02 (Bevacizumab Biosimilar Drug) Versus Avastin® in Combination With Carboplatin and Paclitaxel for the Treatment of Subjects With Stage IIIB/IV Non-squamous Non-Small Cell Lung Cancer (NSCLC)
• Scientific title: STELLA – A Randomized, Multicenter, Multinational, Double-Blind Study to Assess the Efficacy and Safety of MB02 (Bevacizumab Biosimilar Drug) Versus Avastin® in Combination With Carboplatin and Paclitaxel for the Treatment of Subjects With Stage IIIB/IV Non-squamous Non-Small Cell Lung Cancer (NSCLC) - STELLA
• Date of first enrolment: 24/01/2018
• Target sample size: 600
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-001769-26
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: no; Number of treatment arms in the trial: 4
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Brazil, Bulgaria, Chile, Georgia, Greece, Hungary, Lebanon, Malaysia, Peru, Philippines, Russian Federation, Serbia, South Africa, Spain, Thailand, Turkey, Ukraine

Contacts

• Name: Amalia Florez
• Affiliation: mAbxience Research SL

• Name: Amalia Florez
• Affiliation: mAbxience Research SL

Key inclusion & exclusion criteria

Inclusion criteria:
To be eligible for study entry, subjects must satisfy all of the following 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.
3. Subjects should have newly diagnosed or recurrent Stage IIIB/IV (defined by seventh edition of the TNM classification for Lung Cancer, 2010) non-squamous NSCLC not amenable to curative intent surgery, and not have received any systemic therapy for advanced disease (exclusion criteria 3 and 4). For subjects with recurrent disease, at least 6 months must have elapsed before randomization from previous adjuvant treatment. For Stage IV disease, malignant pleural or pericardial effusion must be confirmed by cytological examination if the effusion must be confirmed by cytological examination if the effusion is the only lesion that confirms Stage IV of the disease. In all other cases, the cytological confirmation of effusion is not mandatory.
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 ECOG performance status =1 at Screening.
7. Subjects must have adequate hepatic, renal and hematologic function defined as:
• Hepatic function: bilirubin level <1.5 ULN, ALT and AST levels<2.5×ULN.
• Renal function: serum creatinine level <1.5×ULN, calculated creatinine clearance (CrCl) >50 mL/min (Cockroft-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:
•
Exclusion criteria:
Subjects will be excluded from the study if 1 or more of the following criteria are applicable:
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 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 malignant 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 angi

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

Stage IIIB/IV Non-squamous Non-Small Cell Lung Cancer
MedDRA version: 20.0 Level: LLT Classification code 10079440 Term: Non-squamous non-small cell lung cancer System Organ Class: 100000004864

Intervention(s)

Product Name: MB02
Product Code: MB02
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: bevacizumab
CAS Number: 216974-75-3
Current Sponsor code: MB02
Other descriptive name: BEVACIZUMAB BIOSIMILAR
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-

Trade Name: Avastin
Product Name: Avastin
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: BEVACIZUMAB
CAS Number: 216974-75-3
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-

Primary Outcome(s)

Secondary Objective: The secondary objectives of the study are as follows:
• To evaluate the safety profile of MB02 compared with Avastin® in subjects with Stage IIIB/IV non-squamous NSCLC as per NCI-CTCAE (v4.03).
• To assess the potential immunogenicity of MB02 compared with Avastin® assessed through determination of antidrug antibodies (ADA).
• To assess PFS and OS at cut-off points at Week 18 and at Week 52 compared with those of Avastin®.

Main Objective: The primary objective of the study is to compare the ORR of MB02 and EU approved Avastin® when they are administered in combination with carboplatin and paclitaxel in subjects with Stage IIIB/IV non-squamous NSCLC as assessed according to RECIST

Primary end point(s): Objective Response Rate: Objective response (OR) will be assigned for a subject if the subject displays either complete response (CR) or partial response (PR) per RECIST version 1.1 at Week 18, as assessed by independent review.

Timepoint(s) of evaluation of this end point: Week 18

Secondary Outcome(s)

Secondary end point(s): Secondary Efficacy Endpoints:
Progression Free Survival: PFS will be defined as the time from randomization to subsequent confirmed progression per RECIST version 1.1, measured in weeks and will be determined at Week 18 and at Week 52.
Overall Survival: OS will be defined as the time from randomization to subsequent death, measured in weeks and will be determined at Week 18 and at Week 52.

Timepoint(s) of evaluation of this end point: Week 18 and 52

Secondary ID(s)

2017-001769-26-HU

MB02-C-02-17

Source(s) of Monetary Support

mAbxience

Ethics review

Status: Approved
Approval date: 16/01/2018
Contact: