Analytical characterization, the foundation of all biosimilar programmes, established structural and functional similarity of ABP 980 and trastuzumab RP [7, 8]. PK equivalence from a randomized, single-blind, single-dose, 3‑arm study that compared ABP 980 to trastuzumab RP in healthy subjects (n = 157) demonstrated geometric mean ratios and 90% confidence intervals (CIs) of key PK parameters, maximum serum concentration (Cmax) and area under the plasma concentration-time curve from time 0 to infinity (AUCinf), were contained within a prespecified bioequivalence margin of 0.80 to 1.25 (ABP 980 vs RP-US: 1.04 [0.99–1.08] and 1.06 [1.00–1.12]; ABP 980 vs RP-EU: 0.99 [0.95–1.03] and 1.00 [0.95–1.06]) [9]. Finally, a randomized, multicentre, double-blind, active-controlled clinical trial (LILAC) in women (n = 725) with HER2+ EBC established clinical similarity between ABP 980 and trastuzumab RP [10].

In the primary analysis, based on local pathology review, a higher proportion of subjects in the ABP 980 group achieved pathologic complete response (pCR) versus the RP (48% vs 41%; risk difference [RD]: 7.3%, 90% CI [1.2%−13.4%]; risk ratio [RR]: 1.188, 90% CI 1.033%−1.366%), allowing a conclusion of non-inferiority, see Figure 1a; however, non-superiority could not be confirmed. Nevertheless, sensitivity analyses from central laboratory review confirmed clinical similarity of ABP 980 and the RP (pCR: 48% vs 42%; RD: 5.8%, 90% CI –0.5%-12.0%; RR: 1.142, 90% CI 0.993%–1.312%), see Figure 1b. The study, conducted in both neoadjuvant and adjuvant settings, incorporated a single transition in the adjuvant phase, and demonstrated that switching from the RP to ABP 980 was safe, with similar incidences of adverse events, including cardiac symptoms. No new or unexpected safety signals emerged during neoadjuvant, adjuvant or switch phases, see Table 1, including similar declines in left-ventricular ejection fraction (2.8%, 3.3%, and 3.5% in the ABP 980, RP, and switch groups, respectively) [10, 11]. Immunogenicity, monitored by incidence of anti-drug antibodies, was also similar among patients in the ABP 980 (n = 2), RP (n = 2), and switch (n = 4) groups.

Figure 1: Comparative clinical study results of ABP 980 vs trastuzumab RP in HER2+ early breast cancer: Local (a) and central (b) laboratory evaluation of Total pCR [10]

CI = confidence interval; pCR = pathologic complete response; RD = risk difference; RP = reference product; RR = risk ratio.
Reproduced with permission from von Minckwitz et al, 2018 [10]. [permission received]

These results demonstrated that there were no clinically meaningful differences between ABP 980 and trastuzumab RP in efficacy, safety and immunogenicity. Overall, the TOE supported scientific justification for extrapolation of indications to all approved indications of the RP [6].

Conflict of interest
Several of the authors of the research paper [6] reported conflict of interest, including having received honoraria from, being a consultant for, or being an employee of pharmaceutical companies. For full details of the authors’ conflict of interest, see the research paper [6].

Abstracted by Hans-Christian Kolberg, MD, PhD, Marienhospital Bottrop gGmbH, Bottrop, Germany; and Dr Vladimir Hanes, Amgen Inc, USA.

References
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2. GaBI Online - Generics and Biosimilars Initiative. EU guidelines for biosimilars [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2020 May 15]. Available from: www.gabionline.net/Guidelines/EU-guidelines-for-biosimilars
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10. von Minckwitz G, Colleoni M, Kolberg HC, et al. Efficacy and safety of ABP 980 compared with reference trastuzumab in women with HER2-positive early breast cancer (LILAC study): a randomised, double-blind, phase 3 trial. Lancet Oncol. 2018;19(7):987-98.
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