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Bevacizumab biosimilar candidate TAB008 compared to Avastin® in patients with locally advanced, metastatic EGFR wild-type non-squamous non-small cell lung cancer: a randomized, double-blind, multicenter study

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Abstract

Background

Bevacizumab (Avastin®) is a monoclonal antibody targeting the vascular endothelial growth factor (VEGF). Used alone or in combination with chemotherapy and/or immunotherapy, Avastin® has shown promising efficacy in many cancers. This study compared the efficacy and safety of TAB008 with Avastin® sourced from the EU (bevacizumab-EU), in patients with non-squamous non-small cell lung cancer (nsNSCLC).

Method

In this randomized, double-blind, multicenter, phase III similarity study, treatment naïve for metastatic lung cancer., EGFR wild-type, locally advanced, metastatic, or recurrent non-squamous, non-small cell, lung cancer (nsNSCLC) patients were enrolled and randomized (1:1) into TAB008 or Avastin® groups. Patients received TAB008 or Avastin® 15 mg/kg intravenously plus paclitaxel/carboplatin for 4–6 cycles followed by TAB008 or Avastin® 7.5 mg/kg until disease progression, unacceptable toxicity or death. The primary endpoint compared the objective response rate (ORR) within 6 cycles as read by an independent radiological review committee (IRRC). Secondary endpoints compared disease control rate (DCR) Within 6 cycles, duration of response (DoR), progression-free survival (PFS), a year overall survival rate (OSR), overall survival (OS), safety, immunogenicity, and steady-state pharmacokinetics.

Results

A total of 549 nsNSCLC patients were enrolled (277 in TAB008 group and 272 in Avastin® group). In the full analysis set, ORRs were 55.957% for TAB008 and 55.720% for Avastin®, and the ORR ratio was 1 (90% CI 0.89–1.14), well within the predefined equivalence margin of 0.75–1.33. No significant differences were found in DCR within 6 cycles (95.703% vs 95.367%, p = 0.8536), DoR (8.17 vs 7.3 months, p = 0.3526), PFS (9.10 vs. 7.97 months, p = 0.9457), 1 year overall survival rate (66.2% vs 68%, p = 0.6793), or OS (20.4 vs 17.6 months, p = 0.6549). Serious adverse events (SAEs) occurred in 37.55% (104/277) of patients in the TAB008 group and 34.32% (93/271) in the Avastin® group. Anti-drug antibodies were reported in 3 of 277 (1.08%) TAB008 patients, and 5 of 271 (1.85%) Avastin® patients, neutralizing antibody (Nab) was positive in 1 patient on Avastin®, which became negative upon follow-up. The steady-state trough concentrations (Cssmin) were 106.13 μg/mL in TAB008 group and 96.03 μg/mL in Avastin® groups, with the treatment group ratio of LS geometric means fully contained within the bioequivalence limits of 80.00–125.00% (90% CI was 101.74–120.05%).

Conclusions

TAB008 is similar to Avastin® in terms of efficacy, safety, and pharmacokinetic parameters, with comparable immunogenicity.

Trial registration

ClinicalTrials.gov number; NCT05427305.

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Data Availability

The raw data supporting the conclusions of this manuscript will be made available by the authors, without undue reservation, to any qualified researcher.

References

  • AVASTIN.FDA approval Package Insert. 06/2019

  • Finn RS, Qin S, Ikeda M, Galle PR, IMbrave150 Investigators et al (2020) Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med 382(20):1894–1905

    Article  CAS  PubMed  Google Scholar 

  • Fukuoka M, Wu YL, Thongprasert S et al (2011) Biomarker analyses and final overall survival results from a phase III, randomized, open-label, first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non-small-cell lung cancer in Asia (IPASS). J Clin Oncol 29:2866–2874

    Article  CAS  PubMed  Google Scholar 

  • Garcia J, Hurwitz HI, Sandler AB, Miles D, Coleman RL, Deurloo R, Chinot OL (2020) Bevacizumab (Avastin®) in cancer treatment: a review of 15 years of clinical experience and future outlook. Cancer Treat Rev 86:102017

    Article  CAS  PubMed  Google Scholar 

  • He K, Chen H, Gwise T, Casak S, Lemery S, Keegan P, Pazdur R, Sridhara R (2016) Statistical considerations in evaluating a biosimilar product in an oncology clinical study. Clin Cancer Res 22(21):5167–5170

    Article  PubMed  Google Scholar 

  • Li Y, Li Y, Yang T, Wei S, Wang J, Wang M, Wang Y, Zhou Q, Liu H, Chen J (2013) Clinical significance of EML4-ALK fusion gene and association with EGFR and KRAS gene mutations in 208 chinese patients with non-small cell lung cancer. PLoS ONE 8(1):e52093

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Monk BJ, Lammers PE, Cartwright T et al (2017) Barriers to the Access of Bevacizumab in Patients with Solid Tumors and the Potential Impact of Biosimilars: A Physician Survey. Pharmaceuticals (basel) 10:19

    Article  PubMed  Google Scholar 

  • Sandler A, Gray R, Perry MC et al (2006) Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 355(24):2542–2550

    Article  CAS  PubMed  Google Scholar 

  • Socinski MA, Jotte RM, Cappuzzo F, IMpower150 Study Group et al (2018) Atezolizumab for first-line treatment of metastatic nonsquamous NSCLC. N Engl J Med 378(24):2288–2301

    Article  CAS  PubMed  Google Scholar 

  • Wang J, Qi L, Liu L et al (2019) A phase I, randomized, single-dose study evaluating the biosimilarity of TAB008 to bevacizumab in healthy volunteers. Front Pharmacol 10:905

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang Y, Wu B, Huang L et al (2019) Biosimilar candidate IBI305 plus paclitaxel/carboplatin for the treatment of non-squamous non-small cell lung cancer. Transl Lung Cancer Res 8(6):989–999

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhou C, Wu Y, Chen G et al (2014) Efficacy and biomarker data from BEYOND: A randomized phase 3 study of first line chemotherapy ± bevacizumab in Chinese patients with advanced non-squamous non-small cell lung cancer. Int J Radiat Oncol 90(5):S17

    Article  Google Scholar 

  • Zhu YC, Zhang XG, Lin XP, Wang WX, Li XF, Wu LX, Chen HF, Xu CW, Du KQ (2019) Clinicopathological features and clinical efficacy of crizotinib in Chinese patients with ROS1-positive non-small cell lung cancer. Oncol Lett 17:3466–3474

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

Authors would like to express our deepest gratitude to the patients, in addition to the investigators and staff at the study sites for their contribution to the study. The present study was sponsored by TOT BIOPHARM International Company. All the Authors contributed to revision of the drafts, approved the final version, and made the decision to submit the manuscript for publication.

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Authors and Affiliations

  1. Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China

    S. Lu & Z. Zhou

  2. Cancer Center, Nanjing Jinling Hospital, Nanjing, China

    S. Qin & L. Yang

  3. Oncology, Hunan Cancer Hospital, Changsha, China

    J. Chen

  4. Oncology, First Affiliated Hospital of Anhui Medical University, Hefei, China

    K. Gu

  5. Oncology, Yantai Yuhuangding Hospital, Yantai, China

    P. Sun

  6. Oncology, Anhui Provincial Hospital, Hefei, China

    Y. Pan

  7. Oncology, Weifang People’s Hospital, Weifang, China

    G. Yu

  8. Oncology, Jilin University First Hospital, Jilin, China

    K. Ma

  9. Oncology, Linyi Cancer Hospital, Linyi, China

    J. Shi

  10. Oncology, Jinan Central Hospital, Jinan, China

    Y. Sun

  11. Oncology, Yancheng First People’s Hospital, Yancheng, China

    P. Chen

  12. Oncology, Nanchang University Second Affiliated Hospital, Nanchang, China

    A. Liu

  13. Statistics, The Second Military Medical University, Shanghai, China

    J. He

Authors
  1. S. Lu
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Contributions

SL and SQ designed this protocol of this clinical trial as the leading Principal investigators of the clinical trial, ZZ, JC, KG, PS, YP, GY, KM, JS, YS, LY, PC and AL all participated in the clinical trial as the investigators and wrote the main manuscript text, JH prepared all of the figures and tables as the biostatistician. All authors reviewed the manuscript.

Corresponding author

Correspondence to S. Qin.

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The authors declare no potential conflicts of interest.

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Lu, S., Qin, S., Zhou, Z. et al. Bevacizumab biosimilar candidate TAB008 compared to Avastin® in patients with locally advanced, metastatic EGFR wild-type non-squamous non-small cell lung cancer: a randomized, double-blind, multicenter study. J Cancer Res Clin Oncol 149, 5907–5914 (2023). https://doi.org/10.1007/s00432-022-04563-4

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