CHICAGO ― PF-05280014, a potential biosimilar, was found to have an identical amino acid sequence and similar in vitro functional properties as the monoclonal antibody (mAb) trastuzumab, results of a phase 1, double-blind trial (REFLECTIONS B327-01) reported at the 2013 American Society of Clinical Oncology (ASCO) Meeting.
In this study, PF-05280014 was compared to trastuzumab from the United States (trastuzumab-US) as well as the European Union (trastuzumab-EU), and between the two licensed drugs. Pharmacokinetics (PK), safety, and immune response were also assessed in the trial participants over the course of 70 days.
To test for PK similarity, 105 healthy male volunteers (18-55 years of age) were randomly assigned 1:1:1 to receive a single 6 mg/kg intravenous dose of PF-05280014, trastuzumab-US, or trastuzumab-EU. A test-to-reference comparison was performed, and similarity was considered to be demonstrated if the 90% CI of the test-to-reference ratio of the area under the curve from time 0 to the last time point (AUCT) and maximum concentration (Cmax) were within 80%-125%. The comparison of the 90% CI for all three drugs was within this range.
“The baseline demographics for the 101 subjects evaluable for PK were similar among three treatment arms. The three study drugs exhibited similar characteristics of target-mediated disposition and similar PK parameters,” reported Donghua Yin, PhD, and colleagues at Pfizer, Inc, in Groton, CT. The investigators also noted that the three study drugs showed similar safety profiles.
No serious adverse events (AEs) were experienced, and only four participants had treatment interruptions. Treatment-related AEs reported were similar between the three arms: PF-05280014, 71.4%; trastuzumab-EU, 68.6%; and trastuzumab-US, 65.7%. The incidence of pyrexia in the PF-05280014 arm was higher (n=10) compared with trastuzumab-EU (n=3) and trastuzumab-US (n=2), but the severity was mild and determined not to be a safety concern.
“These PK results also suggest that the three monoclonal mAbs share not only similar disposition properties, but also similar drug-target interaction kinetic characteristics,” the investigators concluded. “These data support the continued development of PF-05280014 as a potential biosimliar to trastuzumab.”