A phase I, randomized, single-dose study evaluating the pharmacokinetic equivalence of biosimilar ABP 215 and bevacizumab in healthy adult men

Abstract

PurposeThis study compared the pharmacokinetic (PK) profiles of the proposed biosimilar ABP 215 with bevacizumab in healthy males.MethodsIn this randomized, single-blind, single-dose, three-arm, parallel-group study, healthy subjects were randomized to receive ABP 215 (n = 68), bevacizumab (US) (n = 67), or bevacizumab (EU) (n = 67) 3 mg/kg intravenously. Primary endpoints were area under the serum concentration–time curve from time 0 extrapolated to infinity (AUCinf) and the maximum observed concentration (C max). Secondary endpoints included safety and immunogenicity.ResultsAUCinf and C max were similar across the three groups. Geometric means ratio (GMR) for C max and AUCinf, respectively, was 0.98 and 0.99 for ABP 215 versus bevacizumab (US); 1.03 and 0.96 for ABP 215 versus bevacizumab (EU); and 1.05 and 0.97 for bevacizumab (US) versus bevacizumab (EU). The 90% confidence intervals for the GMRs of AUCinf and C max were within the prespecified standard PK bioequivalence criteria of 0.80 to 1.25. The incidence of adverse events (AEs) was 47.1, 32.8, and 61.2% in the ABP 215, bevacizumab (US) and bevacizumab (EU) groups, respectively. When analyzed by investigational site, the incidence and severity of AEs were comparable in the ABP 215 and bevacizumab groups. There were no AEs leading to study discontinuation. No binding or neutralizing anti-drug anti-bodies was detected.ConclusionsThis study demonstrated the PK similarity of ABP 215 to both bevacizumab (US) and bevacizumab (EU), and of bevacizumab (US) to bevacizumab (EU). Safety and tolerability were comparable between treatments and no subject developed binding or neutralizing anti-drug anti-bodies.

Efficacy and Safety of the Biosimilar ABP 215 Compared with Bevacizumab in Patients with Advanced Nonsquamous Non–small Cell Lung Cancer (MAPLE): A Randomized, Double-blind, Phase III Study

“…In conclusion, this phase III equivalence study comparing ABP 215 and bevacizumab completes the totality of evidence recommended by regulatory agencies for biosimilars development (7)(8)(9)(10). Together with results of previous studies, the results of this study show that ABP 215 is similar to bevacizumab RP (3,4).…”

“…ABP 215 has been shown to have the same primary and higher-order structure as bevacizumab (3). In addition, high similarity between ABP 215 and bevacizumab has been demonstrated with respect to biological functions in molecular studies and pharmacokinetic parameters in healthy volunteers (3,4). Here, we report the results of a phase III randomized study (MAPLE; registered at ClinicalTrials.gov, NCT01966003) comparing the efficacy, safety, immunogenicity, and pharmacokinetic profiles of ABP 215 and bevacizumab reference product (RP) in patients with advanced nonsquamous NSCLC.…”

A randomized, double-blind, single-dose study to evaluate the biosimilarity of QL1101 with bevacizumab in healthy male subjects

“…In this study, we referred to the research design of similar products abroad, such as PF-06439535 [20], BI-695502 [21], ABP-215 [22] and so on, in which ABP-215 (Mvasi ® ) has been approved by the FDA and the EU. According to previous data [20][21][22][23], we assumed that the coefficient of intra-individual variation was 25%. If the geometric mean ratio (GMR) was set to be 95-105% to achieve 90% power (1-β) at the 5% nominal level (α = 5%), 37 evaluable subjects were required to be in each treatment group to meet the bioequivalence in the range of 80-125.00%.…”

Pivotal Considerations for Optimal Deployment of Healthy Volunteers in Oncology Drug Development

“…The second presentation provided an overview of the general advantages of conducting clinical pharmacology studies in NHVs ( Table ) with the goal of improved equipoise through exposure of fewer end‐of‐life patients to agents of undetermined efficacy. Examples of several targeted oncology agents were provided where up to two doses of the investigational agent were administered to NHVs, usually at the marketed approved doses . The most common AEs were headache, nausea, vomiting, and diarrhea, with only one study reporting serious AEs (SAEs) at the approved dose .…”