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Clinical Trial
. 2021 Jul;35(4):429-444.
doi: 10.1007/s40259-021-00483-w. Epub 2021 Apr 29.

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)

Dmytro Trukhin  1 , Elena Poddubskaya  2 , Zoran Andric  3 , Tamta Makharadze  4 , Ravi Shankar Bellala  5 , Chaiyut Charoentum  6 , Eduardo P Yañez Ruiz  7 , Andrea Fulop  8 , Irfhan Ali Hyder Ali  9 , Kostas Syrigos  10 , Nuran Katgi  11 , Yamil Alonso Lopez Chuken  12 , Ilieva Rumyana  13 , Jasmin Reyes-Igama  14 , Rita de Cassia Costamilan  15 , Ana Del Campo García  16 , Amalia Florez  17 , Alexandra Paravisini  17 , Susana Millan  17 ; STELLA Investigators
Collaborators, Affiliations
Clinical Trial

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)

Dmytro Trukhin et al. BioDrugs. 2021 Jul.

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.

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Conflict of interest statement

SM, AP, AF and ADCG are employees at mAbxience Research SL.

All the other authors declared that they have no conflicts of interest.

Figures

Fig. 1
Fig. 1
Subject disposition
Fig. 2
Fig. 2
Kaplan–Meier plots of (a) progression-free survival, (b) overall survival, (c) duration of response and (d) time to overall response in the intention-to-treat population
Fig. 2
Fig. 2
Kaplan–Meier plots of (a) progression-free survival, (b) overall survival, (c) duration of response and (d) time to overall response in the intention-to-treat population
See this image and copyright information in PMC

References

    1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021 doi: 10.3322/caac.21660. - DOI - PubMed
    1. Desai A, Gyawali B. Financial toxicity of cancer treatment: moving the discussion from acknowledgement of the problem to identifying solutions. E Clin Med. 2020;20:100269. - PMC - PubMed
    1. EMA. Avastin (bevacizumab). Summary of product characteristics 2021. https://www.ema.europa.eu/en/documents/product-information/avastin-epar-.... Accessed 24 Feb 2021.
    1. FDA. Avastin® (bevacizumab) prescribing information. Genentech, Inc, 2021. https://www.gene.com/download/pdf/avastin_prescribing.pdf. Accessed 24 Feb 2021.
    1. National Comprehensive Cancer Network. Clinical practice guidelines in oncology. Non-small cell lung cancer. Version 8.2020. https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf. Accessed 18 Sep 2020.

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