A randomized, single-blind, single-dose study evaluating the pharmacokinetic equivalence of proposed biosimilar ABP 980 and trastuzumab in healthy male subjects.
OBJECTIVE
This study compared the pharmacokinetic (PK) profiles of the proposed biosimilar ABP 980 and trastuzumab in healthy males.


METHODS
In this single-blind study, 157 healthy males were randomized 1:1:1 to a single 6 mg/kg intravenous infusion of ABP 980, FDA-licensed trastuzumab [trastuzumab (US)], or EU-authorized trastuzumab [trastuzumab (EU)]. Primary endpoints were area under the serum concentration-time curve from time 0 to infinity (AUCinf) and maximum observed serum concentration (Cmax). To establish equivalence, the geometric mean ratio (GMR) and 90% confidence interval (CI) for Cmaxand AUCinfhad to be within the equivalence criteria of 0.80-1.25.


RESULTS
The GMRs and 90% CIs for Cmaxand AUCinf, respectively, were: 1.04 (0.99-1.08) and 1.06 (1.00-1.12) for ABP 980 versus trastuzumab (US); 0.99 (0.95-1.03) and 1.00 (0.95-1.06) for ABP 980 versus trastuzumab (EU); and 0.96 (0.92-1.00) and 0.95 (0.90-1.01) for trastuzumab (US) versus trastuzumab (EU). All comparisons were within the equivalence criteria of 0.80-1.25. Treatment-emergent adverse events (TEAEs) were reported in 84.0, 75.0, and 78.2 of subjects in the ABP 980, trastuzumab (US), and trastuzumab (EU) groups, respectively. There were no deaths or TEAEs leading to study discontinuation and no binding or neutralizing anti-drug anti-bodies were detected.


CONCLUSIONS
This study demonstrated the PK similarity of ABP 980 to both trastuzumab (US) and trastuzumab (EU), and of trastuzumab (US) to trastuzumab (EU). No differences in safety and tolerability between treatments were noted; no subject tested positive for binding anti-bodies.
Biosimilars Development, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA, 91320, USA. vhanes@amgen.com.
Vladimir
V
Hanes
Biosimilars Development, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA, 91320, USA.
Vincent
V
Chow
Biosimilars Development, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA, 91320, USA.
Nan
N
Zhang
Biosimilars Development, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA, 91320, USA.
Richard
R
Markus
D000328:Adult; D000906:Antibodies / Q000032:analysis; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D059451:Biosimilar Pharmaceuticals; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D023381:Endpoint Determination; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D016037:Single-Blind Method; D013810:Therapeutic Equivalency; D000068878:Trastuzumab / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D055815:Young Adult
D000906:Antibodies; D000970:Antineoplastic Agents; D059451:Biosimilar Pharmaceuticals; D000068878:Trastuzumab
ABP 980; Biosimilar; HER2; Immunogenicity; Pharmacokinetics; Trastuzumab