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

Sponsor
Mabscale, LLC (Industry)
Overall Status
Not yet recruiting
CT.gov ID
NCT05654454
Collaborator
(none)
620
11
2
48
56.4
1.2

Study Details

Study Description

Brief 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.

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed 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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
620 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
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
Anticipated Study Start Date :
Mar 1, 2023
Anticipated Primary Completion Date :
Dec 1, 2026
Anticipated Study Completion Date :
Mar 1, 2027

Arms and Interventions

Arm Intervention/Treatment
Experimental: Bevacizumab with Paclitaxel and Carboplatin

Patients will begin Period 1 receiving bevacizumab combination therapy (Bevacizumab 15 mg/kg IV + Paclitaxel 175 mg/m2 + IV Carboplatin AUC 6 IV) on Day 0 of Cycle 1 for up to 6 cycles of therapy. Each cycle will consist of 3 weeks (21 days ± 3 days) and a cycle will start with the administration of bevacizumab (produced by Mabscale, LLC). In Period 2, eligible patients will continue to receive bevacizumab (produced by Mabscale, LLC) every 3 weeks as monotherapy.

Drug: Bevacizumab
Bevacizumab 15 mg/kg

Drug: Paclitaxel
Paclitaxel 175 mg/m2

Drug: Carboplatin
Carboplatin AUC 6

Active Comparator: Avastin® with Paclitaxel and Carboplatin

Patients will begin Period 1 receiving bevacizumab combination therapy ( Avastin® 15 mg/kg IV + Paclitaxel 175 mg/m2 IV + Carboplatin AUC 6 IV) on Day 0 of Cycle 1 for up to 6 cycles of therapy. Each cycle will consist of 3 weeks (21 days ± 3 days) and a cycle will start with the administration of bevacizumab (as Avastin®). In Period 2, eligible patients will continue to receive bevacizumab (Avastin®) every 3 weeks as monotherapy.

Drug: Bevacizumab
Bevacizumab 15 mg/kg

Drug: Paclitaxel
Paclitaxel 175 mg/m2

Drug: Carboplatin
Carboplatin AUC 6

Outcome Measures

Primary Outcome Measures

  1. Objective Response Rate (ORR) at Week 18 [18 weeks from randomisation]

    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).

Secondary Outcome Measures

  1. Progression-free Survival (PFS) [At week 18 and 42 from randomisation]

    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.

  2. Overall Survival (OS) [At week 18 and 42 from randomisation]

    Overall survival was defined as the time from randomization to subsequent death, measured in weeks and months.

  3. Duration of response (DOR) [48 weeks]

    Duration of responce was defined as the time from responce to treatment till progression or death.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Arkhangelsk Clinical Oncological Dispensary Arkhangel'sk Russian Federation
2 State Budget Healthcare Institution Ivanovo Regional Oncology Dispensary Ivanovo Russian Federation
3 Kaluga Regional Clinical Oncology center Kaluga Russian Federation
4 Regional clinical oncological dispensary n.a.Sigal Kazan' Russian Federation
5 Hadassah Medical Moscow Moscow Russian Federation
6 National Medical Oncology Research Center n.a. N.N. Blokhina Moscow Russian Federation
7 Novosibirsk oncologic dispensary Novosibirsk Russian Federation
8 Omsk clinical oncologic dispensary Omsk Russian Federation
9 National Medical Research Center of Oncology N.A. N.N. Petrov Saint Petersburg Russian Federation
10 Medical University "Reaviz" Samara Russian Federation
11 Smolensk oncologic dispensary Smolensk Russian Federation

Sponsors and Collaborators

  • Mabscale, LLC

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Mabscale, LLC
ClinicalTrials.gov Identifier:
NCT05654454
Other Study ID Numbers:
  • BEV-III/2022
First Posted:
Dec 16, 2022
Last Update Posted:
Dec 16, 2022
Last Verified:
Dec 1, 2022
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of Dec 16, 2022