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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03296163
• Date of registration: 19/09/2017
• Prospective Registration: Yes
• Primary sponsor: mAbxience S.A
• Public title: A Study Comparing MB02 and Avastin® in Subjects With Stage IIIB/IV Non-Squamous Non-Small Cell Lung Cancer (NSCLC) STELLA
• Scientific title: 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)
• Date of first enrolment: February 6, 2018
• Target sample size: 627
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03296163
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Care Provider, Investigator).
• Phase: Phase 3

Countries of recruitment

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

Key inclusion & exclusion 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.

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.

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) >30 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 < 100 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, vasectomised 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 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).

Exclusion Criteria:

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 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: hepatitis B, hepatitis C, or HIV.

13. Subjects who are pregna


Age minimum: 18 Years
Age maximum: 80 Years
Gender: All

Health Condition(s) or Problem(s) studied

Non-small Cell Lung Cancer

Intervention(s)

Drug: EU-approved Avastin®

Drug: MB02 (Bevacizumab Biosimilar Drug)

Drug: Paclitaxel

Drug: Carboplatin

Primary Outcome(s)

Objective Response Rate (ORR) at Week 18 [Time Frame: 18 weeks from randomisation]

Secondary Outcome(s)

Immunogenicity Assessments (Anti-drug Antibodies) [Time Frame: At Weeks 1, 3, 9, 18, 34 and 52 from randomisation and, at the End of Treatment Visit if, an ADA sample has not been collected within the previous 3 weeks]

Immunogenicity Assessments (Neutralizing Antibodies) [Time Frame: At Weeks 1, 3, 9, 18, 34 and 52 from randomisation and, at the End of Treatment Visit if, an Nab sample has not been collected within the previous 3 weeks]

Comparison of Safety profile (incidence, nature, and severity of adverse events (AEs) graded according to NCI-CTCAE; v4.03) [Time Frame: Week 1 to week 52]

Overall survival (OS) at Week 18 and at Week 52 [Time Frame: At Week 18 and at Week 52 from randomisation]

Progression-free survival (PFS) at Week 18 and at Week 52 [Time Frame: At Week 18 and at Week 52 from randomisation]

Secondary ID(s)

MB02-C-02-17

Source(s) of Monetary Support

Please refer to primary and secondary sponsors