A Safety and Efficacy Study of Bevacizumab, Paclitaxel, Carboplatin Compared to Avastin® in Non-Small Cell Lung Cancer

Non-Small Cell Lung Cancer Clinical Trial

Official title:

Randomized Double Blind Phase III Trial Comparing Safety and Efficacy of Bevacizumab (Mabscale LLC, Russia) + Paclitaxel + Carboplatin to Avastin® + Paclitaxel + Carboplatin in Inoperable or Advanced Non-squamous Non-small-cell Lung Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05654454
• Other study ID #: BEV-III/2022
• Status: Recruiting
• Phase: Phase 3
• Start date: May 31, 2023
• Est. completion date: March 2027

Study information

• Verified date: June 2024
• Source: Mabscale, LLC
• Contact: Alexander BORISOV, MD
• Phone: +74997149289
• Email: borisov.a[@]benerix.ru
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

BEV-III/2022 is a double-blind randomized multicenter clinical trial comparing efficacy of bevacizumab (manufactured by Mabscale, LLC) and paclitaxel plus carboplatin to Avastin® and paclitaxel plus carboplatin in first-line treatment for patients with advanced (unresectable, locally advanced, recurrent or metastatic) non-squamous NSCLC. The purpose of the study is to demonstrate equivalence of efficacy and safety of bevacizumab (manufactured by Mabscale, LLC) to Avastin®. Study includes pharmacokinetics assessment.

Description:

Bevacizumab is a monoclonal antibody currently being developed by Mabscale LLC, as a proposed biosimilar to Avastin®, which is approved as first line treatment in combination with carboplatin and paclitaxel for patients with unresectable, locally advanced, recurrent or metastatic non-squamous Non-Small Cell Lung Cancer. This randomized equivalence study is designed to meet the regulatory requirement for approval of a biosimilar product.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 620
• Est. completion date: March 2027
• Est. primary completion date: December 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Written informed consent

• Male and female patients at least 18 years of age

• Newly diagnosed Stage IIIB/C or IV non-small cell lung cancer (according to Revised Cancer Staging by American Joint Committee on Cancer (AJCC) and the International Union Against Cancer (UICC) 8th edition) or recurrent non-small cell lung cancer (NSCLC)

• Histologically or cytologically confirmed diagnosis of predominately non-squamous NSCLC

• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

• Be eligible to receive study treatment of bevacizumab, paclitaxel, and carboplatin based on local standard of care, for the treatment of advanced or metastatic non-squamous NSCLC

• Presence of at least 1 measurable tumour as defined by modified Response Evaluation Criteria in Solid Tumors (RECIST 1.1)

• Neutrophils = 1,5 × 10^9/L

• Platelets = 100 × 10^9/L

• Haemoglobin = 90 g/L

• Bilirubin level = 1.5 × upper limit of normal (ULN)

• Aspartate-aminotransferase (AST) and alanine-aminotransferase (ALT) levels < 3 × ULN (< 5 × ULN for patients with liver metastases)

• Alkaline phosphatase level < 3 × ULN (< 5 × ULN for patients with liver or bone metastases)

Exclusion Criteria:

• Known sensitizing EGFR mutations or ALK translocation positive mutations

• Evidence of a tumor that compresses or invades major blood vessels or tumor cavitation that is likely to bleed

• Major surgery 28 days before inclusion into the study

• Minor surgery 7 days before inclusion into the study

• Stage II or higher of neuropathy or ototoxicity according to Common Terminology Criteria for Adverse Events (CTCAE) v.5.0, excluding trauma

• Life expectancy less than 6 months

• Metastases to central nervous system or carcinomatous meningitis

• Pregnancy or lactation

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small Cell Lung Cancer

Intervention

Drug:
• Bevacizumab
Bevacizumab 15 mg/kg
• Paclitaxel
Paclitaxel 175 mg/m2
• Carboplatin
Carboplatin AUC 6

Locations

Country	Name	City	State
Russian Federation	Arkhangelsk Clinical Oncological Dispensary	Arkhangel'sk
Russian Federation	State Budget Healthcare Institution Ivanovo Regional Oncology Dispensary	Ivanovo
Russian Federation	Kaluga Regional Clinical Oncology Dispensary	Kaluga
Russian Federation	Regional clinical oncological dispensary n.a.Sigal	Kazan'
Russian Federation	Burdenko Main Military Clinical Hospital	Moscow
Russian Federation	Hadassah Medical Moscow	Moscow
Russian Federation	National Medical Oncology Research Center n.a. N.N. Blokhina	Moscow
Russian Federation	Murmansk Regional Clinical Hospital	Murmansk
Russian Federation	Nizhny Novgorod Regional Oncology Dispensary	Nizhny Novgorod
Russian Federation	Novosibirsk oncologic dispensary	Novosibirsk
Russian Federation	Omsk clinical oncologic dispensary	Omsk
Russian Federation	Perm Regional Clinical Hospital	Perm
Russian Federation	Euromedservice medical center	Pushkin
Russian Federation	Clinical Hospital RZD-Medicine	Saint Petersburg
Russian Federation	Euro Cityclinic	Saint Petersburg
Russian Federation	Leningrad regional clinical hospital	Saint Petersburg
Russian Federation	Leningrad regional clinical hospital (prev.Oncological dispensary n.a.Roman)	Saint Petersburg
Russian Federation	National Medical Research Center of Oncology N.A. N.N. Petrov	Saint Petersburg
Russian Federation	Northwestern Center for Evidence-Based Medicine	Saint Petersburg
Russian Federation	Medical University "Reaviz"	Samara
Russian Federation	Smolensk oncologic dispensary	Smolensk
Russian Federation	Smolensk Regional Clinical Hospital	Smolensk
Russian Federation	Tverskoy Regional Oncological Dispensary	Tver
Russian Federation	Oblastnoy Clinical Oncological Dispansery	Veliki Nóvgorod
Russian Federation	Volgograd Regional Clinical Oncology Dispensary	Volgograd
Russian Federation	Regional Clinical Oncological Hospital	Yaroslavl

Sponsors (1)

Lead Sponsor	Collaborator
Mabscale, LLC

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate (ORR) at Week 18	Objective response rate was assigned for a subject if the subject displayed either complete response (CR) or partial response (PR) per RECIST version 1.1 at Week 18, as assessed by independent radiological review committee (IRC).	18 weeks from randomisation
Secondary	Progression-free Survival (PFS)	Progression-free survival was defined as the time from randomization to subsequent confirmed progression per RECIST version 1.1, or death (whichever occurred first), measured in weeks and months. For PFS assessment clinical progression (i.e., treatment discontinuation due to progression of disease) was also considered as an event.	At week 18 and 42 from randomisation
Secondary	Overall Survival (OS)	Overall survival was defined as the time from randomization to subsequent death, measured in weeks and months.	At week 18 and 42 from randomisation
Secondary	Duration of response (DOR)	Duration of responce was defined as the time from responce to treatment till progression or death.	48 weeks