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)

Trukhin D 1 , Poddubskaya E 2 , Andric Z 3 , Makharadze T 4 , Bellala RS 5 , Charoentum C 6 Show all authors , Yañez Ruiz EP 7 , Fulop A 8 , Hyder Ali IA 9 , Syrigos K 10 , Katgi N 11 , Lopez Chuken YA 12 , Rumyana I 13 , Reyes-Igama J 14 , Costamilan RC 15 , Del Campo García A 16 , Florez A 17 , Paravisini A 17 , Millan S 17 , STELLA Investigators

Affiliations 

  • 1 Day Patient Facility of Dispensary and Policlinic Department, Odessa Regional Oncological Dispensary, Odessa, Ukraine
  • 2 VitaMed, LLC, Moscow, Russia
  • 3 Clinical Hospital Center, Bezanijska kosa Bezanijska kosa bb, Beograd, Serbia
  • 4 Ltd High Technology Hospital Medcenter, Batumi, Adjara, Georgia
  • 5 Queens NRI Hospital, Visakahapatnam, India
  • 6 Maharaj Nakorn Chiang Mai Hospital, Faculty of Medicine, Chiang Mai University, Muang, Chiang Mai, Thailand
  • 7 Oncology-Hematology Unit. Department of Internal Medicine. School of Medicine, Clinical Research Center SIM, University of the Frontera, Temuco, Chile
  • 8 Orszagos Koranyi Pulmonologiai Intezet, VI. Tudobelosztaly, Budapest, Hungary
  • 9 Respiratory Department, Hospital Pulau Pinang, George Town, Pinang, Malaysia
  • 10 Department of Internal Medicine, Sotiria General Hospital for Chest Diseases, Athens, Greece
  • 11 Dr. Suat Seren Chest Diseases and Chest Surgery Training and Research Hospital, Health Sciences University, Izmir, Yenisehir, Turkey
  • 12 Hospital Universitario "Dr. Jose Eleuterio Gonzalez" (Centro Universitario contra el Cancer), Monterrey, Nuevo Leon, Mexico
  • 13 Plovid Department of Medical Oncology, Multiprofile Hospital for Active Treatment Central Onco Hospital OOD, Plovdiv, Bulgaria
  • 14 Baguio General Hospital and Medical Center. Baguio city, Benguet, Philippines
  • 15 Fundacao Universidade de Caxias do Sul, Instituto de Pesquisas Clinicas para Estudos Multicentricos, IPCEM, Caxias do Sul, Brazil
  • 16 mAbxience Research S.L., Madrid, Spain. ana.delcampo@mabxience.com
  • 17 mAbxience Research S.L., Madrid, Spain
BioDrugs, 2021 Jul;35(4):429-444.
PMID: 33914256 DOI: 10.1007/s40259-021-00483-w

Abstract

BACKGROUND: MB02 (bevacizumab biosimilar) showed similar structural, functional, and pharmacokinetic properties to reference bevacizumab (Avastin®; EU-bevacizumab).

OBJECTIVES: To confirm clinical similarity between MB02 and EU-bevacizumab, a comparability study was undertaken in the first-line treatment of stage IIIB/IV non-squamous non-small cell lung cancer (NSCLC).

PATIENTS AND METHODS: This multinational, double-blind, randomized, phase III study (STELLA) compared MB02 or EU-bevacizumab (15 mg/kg) administered with chemotherapy (paclitaxel 200 mg/m2 and carboplatin AUC6) on Day 1 of every 3-week cycle for 6 cycles (Week 18), followed by MB02/EU-bevacizumab in blinded monotherapy until disease progression, unacceptable toxicity, death, withdrawal of consent or end of study (Week 52). The primary efficacy endpoint was objective response rate (ORR) evaluated by an independent radiological review committee (IRC) at Week 18 (intent-to-treat population). Secondary endpoints included progression-free survival (PFS), overall survival (OS), safety and immunogenicity.

RESULTS: A total of 627 subjects were randomized 1:1 to MB02 (n = 315) or EU-bevacizumab (n = 312). ORR, assessed by the IRC at Week 18, was comparable in MB02 (40.3%) and EU-bevacizumab (44.6%) groups. ORR risk ratio of 0.910 (90% CI 0.780 to 1.060; 95% CI 0.758 to 1.092) and ORR risk difference of -4.02 (90% CI -10.51 to 2.47; 95% CI -11.76 to 3.71) were within the similarity predefined margins. There were no significant differences between MB02 and EU-bevacizumab groups in median PFS (36.0 vs 37.3 weeks, respectively; HR 1.187; 95% CI 0.98 to 1.44) and median OS (not achieved; HR 1.108; 95% CI: 0.83 to 1.49) at the end of study. The safety profile of MB02 and EU-bevacizumab regarding nature, frequency and severity of the adverse events (AE) was comparable. The most frequent grade ≥3 investigational-product-related AEs were hypertension and anemia, with a difference between treatment groups of <5%. Anti-drug antibodies (ADA) and neutralizing ADA (NAb) incidence were similar in both treatment groups.

CONCLUSION: MB02 demonstrated similar efficacy to EU-bevacizumab, in combination with carboplatin and paclitaxel, in subjects with advanced non-squamous NSCLC, with comparable safety and immunogenicity profiles.

CLINICAL TRIAL REGISTRATION: EudraCT No. 2017-001769-26; ClinicalTrials.gov: NCT03296163.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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