*Monoclonal Antibodies for Cancer Treatment DOI: http://dx.doi.org/10.5772/intechopen.97915*

Finally, when all tests are done and the authorization holder will submit the documents to receive the marketing authorization, it can be extrapolating all indications from the reference product to the biosimilar. When biosimilar comparability has been demonstrated in one indication, extrapolation of clinical data to other indications of the reference product could be acceptable but needs to be scientifically justified. It is expected that the safety and efficacy can be extrapolated when biosimilar comparability has been demonstrated in all aspects described before [19, 23, 29].

This condition is not applied in all situations. For example, if a reference monoclonal antibody is licensed both as an immunomodulator and as an anticancer antibody, the scientific justification as regards extrapolation between the two indication is more challenging and may have to involve more specific studies [29].

### **6. Conclusions**

Since monoclonal antibodies play an essential role in cancer treatment and are responsible for high healthcare costs, the development of biosimilars is particularly important in oncology. Several biosimilars of the monoclonal antibodies trastuzumab, rituximab, and bevacizumab have been approved and began to be marketed in Europe, EUA and other countries around the world. More diversification of monoclonal antibodies biosimilars is expected in the next years, as the patent of other molecules will expire.

The biosimilar development pathway consists of a comprehensive comparability exercise between the biosimilar candidate and the reference product, primarily focusing on data from analytical studies. Clinical studies for biosimilar candidates follow a different design to those for a new biological. Adequate information on the biosimilar approval pathway, the robustness of overall evidence used to demonstrate biosimilarity, and how the clinical development of a biosimilar is done is important for all: professional, patient, governments, and other stakeholders.

### **Conflict of interest**

Annemeri Livinalli: is involved in consulting, advisory work and speaking engagements for Amgen, Sandoz, Teva, Servier, Dr. Reddy's, Accord, United Medical, Achè. Taís Freire Galvão: The author declares no conflict of interest.

### **Author details**

Annemeri Livinalli\* and Taís Freire Galvão State University of Campinas, Campinas, Brazil

\*Address all correspondence to: annemeri.livinalli@gmail.com

© 2021 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

*Monoclonal Antibodies for Cancer Treatment DOI: http://dx.doi.org/10.5772/intechopen.97915*

## **References**

[1] Moraes JZ, Hamaguchi B, Braggion C, et al. Hybridoma technology: is it still useful? Curr Res Immunol 2021; 2: 32-40.

[2] Manis JP. Overview of therapeutic monoclonal antibodies. In: Post TW (ed) *UpToDate*. Waltham, MA: UpToDate 2021.

[3] Ryman JT, Meibohm B. Pharmacokinetics of Monoclonal Antibodies. CPT Pharmacometrics Syst Pharmacol 2017; 6: 576-588.

[4] Zahavi D, Weiner L. Monoclonal Antibodies in Cancer Therapy. Antibodies 2020; 9: 34.

[5] Castelli MS, McGonigle P, Hornby PJ. The pharmacology and therapeutic applications of monoclonal antibodies. Pharmacol Res Perspect 2019; 7: 535.

[6] Weiner LM, Surana R, Wang S. Monoclonal antibodies: versatile platforms for cancer immunotherapy. Nat Rev Immunol 2010; 10: 317-327.

[7] European Medicines Agency. *Guideline on the evaluation of anticancer medicinal products in man*. 2012.

[8] WHO Collaborating Centre for Drug Statistics Methodology. ATC classification system - other antineoplastic agents: monoclonal antibodies, https://www.whocc.no/ atc\_ddd\_index/?code=L01XC (2020, accessed 24 February 2021).

[9] Lu RM, Hwang YC, Liu IJ, et al. Development of therapeutic antibodies for the treatment of diseases. J Biomed Sci 2020; 27: 1-30.

[10] Kunert R, Reinhart D. Advances in recombinant antibody manufacturing. Appl Microbiol Biotechnol 2016; 100: 3451-3461.

[11] Strohl WR. Current progress in innovative engineered antibodies. Protein Cell 2018; 9: 86-120.

[12] Gerriets V, Kasi A. *Bevacizumab*. Treasure Island (FL): StatPearls [Internet], 2020.

[13] Smith MR. Rituximab (monoclonal anti-CD20 antibody): mechanisms of action and resistance. DOI: 10.1038/ sj.onc.1206939.

[14] Greenblatt K, Khaddour K. *Trastuzumab*. Treasure Island (FL): StatPearls [Internet], 2020.

[15] Akbari V, Chou CP, Abedi D. New insights into affinity proteins for HER2-targeted therapy: Beyond trastuzumab. Biochimica et Biophysica Acta - Reviews on Cancer 2020; 1874: 188448.

[16] Busse A, Lüftner D. What Does the Pipeline Promise about Upcoming Biosimilar Antibodies in Oncology? Breast Care 2019; 14: 10-16.

[17] European Medicines Agency. *Guideline on similar biological medicinal products containing biotechnology-derived proteins as active substance : quality issues*. 2014.

[18] European Medicines Agency. *ICH guideline Q 8 (R2) on Pharmaceutical Development,*. 2017.

[19] European Medicines Agency. *Guideline on similar biological medicinal products containing biotechnology-derived proteins as active substance: non-clinical and clinical issues*. 2014. Epub ahead of print 2014. DOI: 10.1089/ blr.2011.9970.

[20] Food and Drug Administration. *Quality Considerations in Demonstrating Biosimilarity of a Therapeutic Protein Product to a Reference Product*. 2015.

[21] Food and Drug Administration. *Clinical Pharmacology Data to Support a Demonstration of Biosimilarity to a Reference Product*. 2016.

[22] Sullivan PM, Digrazia LM. Analytic characterization of biosimilars. Am J Heal Pharm 2017; 74: 568-579.

[23] Food and Drug Administration. *Scientific Considerations in Demonstrating Biosimilarity to a Reference Product*. 2015.

[24] European Medicines Agency. *Note for guidance on specifications: test procedures and acceptance criteria for biotechnological/biological products*. 1999. Epub ahead of print 1999. DOI: 10.1093/ elt/40.2.121.

[25] Baldo BA. *Safety of Biologics Therapy*. Switzerland: Springer International Publishing, 2016. Epub ahead of print 2016. DOI: 10.1007/978-3-319-30472-4.

[26] Chiu ML, Goulet DR, Teplyakov A, et al. Antibody Structure and Function: The Basis for Engineering Therapeutics. Antibodies 2019; 8: 55.

[27] Goetze AM, Schenauer MR, Flynn GC. mAbs Assessing monoclonal antibody product quality attribute criticality through clinical studies. *Rev mAbs*; 2: 500-507.

[28] Food and Drug Administration. *Development of Therapeutic Protein Biosimilars: Comparative Analytical Assessment and Other Quality-Related Considerations*. 2019.

[29] European Medicines Agency. *Guideline on similar biological medicinal products containing monoclonal antibodies - non-clinical and clinical issues*. 2012.

[30] Ishii-Watabe A, Kuwabara T. Biosimilarity assessment of biosimilar therapeutic monoclonal antibodies. Drug Metab Pharmacokinet 2019; 34: 64-70.

[31] European Medicines Agency. *Assessment report of Herzuma*. 2017.

[32] European Medicines Agency. *Assessment report of Aybintio*. 2020.

[33] European Medicines Agency. *Assessment report of Ruxience*. 2020.

[34] Food and Drug Administration. Product Information: Rituxan, https:// www.accessdata.fda.gov/drugsatfda\_ docs/label/1997/ritugen112697-lab.pdf (accessed 11 January 2021).

[35] Food and Drug Administration. *Clinical Trial Endpoints for the Approval of Cancer Drugs and Biologics: Guidance for Industry*. 2019.

[36] Wolff-Holz E, Tiitso K, Vleminckx C, et al. Evolution of the EU Biosimilar Framework: Past and Future. BioDrugs 2019; 33: 621-634.

[37] World Health Organization. *Guidelines on evaluation of monoclonal antibodies as similar biotherapeutic roducts (SBPs)*. 2016.

[38] Center for Drug Evaluation and Research. *Summary Review for regulatory action: Mvasi*. 2017.

[39] Center for Drug Evaluation and Research. *Summary Review for regulatory action: Zirabev*. 2019.

[40] European Medicines Agency. *Assessment report: Equidacent*. 2020.

[41] European Medicines Agency. *Assessment report: Aybintio*. 2020.

[42] Niederwieser D, Hamm C, Cobb P, et al. Efficacy and Safety of ABP 798: Results from the JASMINE Trial in Patients with Follicular Lymphoma in Comparison with Rituximab Reference Product. Target Oncol 2020; 15: 599-611.

[43] Sharman JP, Liberati AM, Ishizawa K, et al. A Randomized, *Monoclonal Antibodies for Cancer Treatment DOI: http://dx.doi.org/10.5772/intechopen.97915*

Double-Blind, Efficacy and Safety Study of PF-05280586 (a Rituximab Biosimilar) Compared with Rituximab Reference Product (MabThera®) in Subjects with Previously Untreated CD20-Positive, Low-Tumor-Burden Follicular Lymphoma (LTB-FL). BioDrugs 2020; 34: 171-181.

[44] Center for Drug Evaluation and Research. *Summary review: Truxima*. 2018.

[45] European Medicines Agency. *Assessment report: Riximyo*. 2017.

[46] European Medicines Agency. *Assessment report: Blitzima*. 2017.

[47] European Medicines Agency. *Assessment report: Rixathon*. 2017.

[48] European Medicines Agency. *Assessment report: Ritemvia*. 2017.

[49] Food and Drug Administration. *Summary review: Ogivri*. 2017.

[50] Center for Drug Evaluation and Research. *Summary review: trazimera*. 2019.

[51] Center for Drug Evaluation and Research. *Clinical reviews: Kanjinti*. 2019.

[52] Center for Drug Evaluation and Research. *Summary review: Ontruzant*. 2019.

[53] Center for Drug Evaluation and Research. *Summary review: Herzuma*. 2018.

[54] European Medicines Agency. *Assessment report: Zercepac*. 2020.

[55] Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). Eur J Cancer 2009; 45: 228-247.

[56] European Medicines Agency. *Guideline on immunogenicity assessment of therapeutic proteins*. 2017.

[57] Food and Drug Administration. *Immunogenicity assessment for therapeutic protein products*. 2014.

[58] Food and Drug Administration. *Immunogenicity testing of therapeutic protein products — developing and validating assays for anti-drug antibody detection*. 2019.

[59] European Medicines Agency. *Guideline on immunogenicity assessment of monoclonal antibodies intended for in vivo clinical use . Guideline on immunogenicity assessment of monoclonal antibodies intended for in vivo clinical use. Table of contents*. 2012.
