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)

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 EUbevacizumab (15 mg/kg) administered with chemotherapy (paclitaxel 200 mg/m 2 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.The members of the STELLA study investigators are listed in Online Resource 1 and in the Acknowledgements section.Extended author information available on the last page of the article care costs [1,2]. Avastin ® , the reference bevacizumab, has been approved for use in many cancer indications and settings, including first-line treatment of advanced NSCLC in combination with other chemotherapeutic agents [3,4]. Several international guidelines recommend the use of bevacizumab in association with chemotherapy in first-line and maintenance settings in advanced NSCLC [5,6]. In addition, recent evidence points to novel combinations of bevacizumab with new molecular therap...

A randomized, double blind, single dose, comparative study of the pharmacokinetics, safety and immunogenicity of MB02 (bevacizumab biosimilar) and reference bevacizumab in healthy male volunteers

“…Due to the absence of pharmacodynamic markers for bevacizumab that can be related to patient outcome, a comparative study designed to demonstrate similar clinical efficacy between MB02, US‐bevacizumab and EU‐bevacizumab was required to confirm efficacy 19 . The clinical development of MB02 continues with 1 pivotal Phase III clinical study in patients with non‐small cell lung cancer, which has been published recently 20 . In the non‐small cell lung cancer study, the efficacy and safety MB02 were comparable to the reference bevacizumab.…”

“…Therefore, MB02 can be considered bioequivalent to reference bevacizumab in healthy male subjects and there is no particular reason to suspect different safety recently. 20 In the non-small cell lung cancer study, the efficacy and safety MB02 were comparable to the reference bevacizumab.…”

A randomized, single-dose, pharmacokinetic equivalence study comparing MB02 (proposed biosimilar) and reference bevacizumab in healthy Japanese male volunteers

“…The safety and immunogenicity profile were also similar for all three treatment groups. Furthermore, considering that there is no a significant effect of ethnicity on PK this study allows to extrapolate the recent results from the pivotal clinical equivalence study in 627 NSCLC patients included in the global clinical package for MB02 (ClinicalTrials.gov NCT03296163) [24] to Japanese population.…”

Efficacy and Safety of Bevacizumab Biosimilars Compared With Reference Biologics in Advanced Non-small Cell Lung Cancer or Metastatic Colorectal Cancer Patients: A Network Meta-Analysis

“…A total of 402 records from the above databases were identified, 17 reports in the full text were reviewed, and 10 RCTs with 5472 patients were deemed eligible for the criteria above ( Figure 1 ) ( Romera et al, 2018 ; Reinmuth et al, 2019 ; Thatcher et al, 2019 ; Yunpeng Yang et al, 2019 ; Reck et al, 2020 ; Rezvani et al, 2020 ; Qin et al, 2021 ; Shi et al, 2021 ; Syrigos et al, 2021 ; Trukhin et al, 2021 ). The baseline characteristics of these trials were summarized in Table 1 .…”

“…For NSCLC, all patients received the same medication regimen: one of the bevacizumab biosimilars or reference biologics (15 mg/kg) along with carboplatin (AUC 6) and paclitaxel (175/200 mg/m 2 ) once 3 weeks. Related biosimilars above mainly involved seven different types, including PF-06439535 (Zirabev TM ) ( Reinmuth et al, 2019 ), ABP 215 (Mvasi TM ) ( Thatcher et al, 2019 ), SB8 (Aybintio TM ) ( Reck et al, 2020 ), FKB238( Syrigos et al, 2021 ), MB02 (Alymsys TM ) ( Trukhin et al, 2021 ), IBI305 (Byvasda TM ) ( Yunpeng Yang et al, 2019 ), and LY01008 (Boyounuo TM ) ( Shi et al, 2021 ). At present, all biosimilars except FKB238 have been approved to market in the clinical environment.…”