Abstract P6-13-12: Comparative similarity of ABP 980 and trastuzumab: Results of functional similarity and human pharmacokinetic assessment

Abstract

Abstract Background: ABP 980 is being developed as a biosimilar to trastuzumab, a monoclonal antibody (mAb) that binds human epidermal growth factor receptor 2 (HER2), resulting in proliferation inhibition (PI) and induction of antibody-dependent cell-mediated cytotoxicity (ADCC). Biosimilar mAbs are likely to have minor differences with the reference product due to variances in expression systems, bioprocess, and purification; demonstration of analytical, pharmacologic, and pharmacokinetic (PK) similarity is the foundation for biosimilarity. Functional (PI, ADCC, and tumor xenograft models) and PK similarity between ABP 980 and EU-authorized trastuzumab reference product has been previously evaluated. Objective: To demonstrate functional and PK similarity between ABP 980 and FDA-licensed trastuzumab reference product. Methods: Potency of ABP 980 and FDA-licensed trastuzumab was compared by measuring PI and recombinant HER2 (rHER2) binding affinity. PI activity was evaluated using BT-474 cells. Surface plasmon resonance analysis was used to determine the equilibrium binding affinity (Kd) to rHER2. PK similarity was evaluated in a randomized, single-blind, single-dose, parallel-group study in healthy adult men. Primary endpoints were area under the serum concentration-time curve from time 0 to infinity (AUCinf) and maximum observed serum concentration (Cmax). Secondary endpoints were safety, tolerability, and immunogenicity. Results: ABP 980 displayed PI and rHER2 binding activities comparable to trastuzumab. The range of relative potency by PI was 82%–114% for ABP 980 and 91%–116% for trastuzumab. The Kd ranged from 75–79 pM for ABP 980 and 67–80 pM for trastuzumab. PK similarity was demonstrated for the comparison of ABP 980 with trastuzumab. The geometric mean (GM) ratios for Cmax and AUCinf were 1.04 (90% CI, 0.995–1.079) and 1.06 (90% CI, 0.997–1.117). Both CIs fell within the standard prespecified bioequivalence criteria of 0.80–1.25. After 6 mg/kg intravenous infusion, the GM of Cmax and AUCinf were 135.90 µg/mL and 34061.43µg·h/mL for ABP 980 and 131.19µg/mL and 32271.67µg·h/mL for trastuzumab. The incidence of treatment-emergent adverse events (TEAEs) was comparable between treatment groups. TEAEs occurred in 84% subjects receiving ABP 980 and 75% of subjects receiving trastuzumab; no anti-drug antibodies were detected. Conclusions: ABP 980 has been shown to be similar to FDA-licensed trastuzumab in functional tests and binding affinity to antigen, as well as in a phase 1 human PK study. Citation Format: Hanes V, Born T, Chow V, Zhang N, Howard M, Schulz A, Markus R. Comparative similarity of ABP 980 and trastuzumab: Results of functional similarity and human pharmacokinetic assessment. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-13-12.