A phase I pharmacokinetics trial comparing PF-05280014 (a potential biosimilar) and trastuzumab in healthy volunteers (REFLECTIONS B327-01).

Breast Cancer - HER2/ER
Session Type and Session Title: 
General Poster Session, Breast Cancer - HER2/ER
Abstract Number: 
J Clin Oncol 31, 2013 (suppl; abstr 612)
Donghua Yin, Kerry B Barker, Ruifeng Li, Xu Meng, Steven D Reich, Alejandro D Ricart, Dan Rudin, Carrie T Taylor, Charles M. Zacharchuk, Arne G Hansson; Pfizer Inc., San Diego, CA; Pfizer Inc., Cambridge, MA; Pfizer Inc., Buenos Aires, Argentina; Pfizer Inc., New Haven, CT; Pfizer Inc., North Branford, CT

Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).

Abstract Disclosures


Background: PF-05280014, a proposed biosimilar to trastuzumab, has an identical amino acid sequence and similar physicochemical and in vitro functional properties to trastuzumab. This study was designed to demonstrate PK similarity of PF-05280014 to trastuzumab from the US (trastuzumab-US) and EU (trastuzumab-EU), and between the licensed drugs. Safety and immunogenicity were also evaluated. Methods: In this double-blind trial (NCT01603264), 105 healthy male volunteers, 18-55 years old were randomized 1:1:1 to receive a single 6 mg/kg IV dose of PF-05280014, trastuzumab-US or trastuzumab-EU. All subjects provided informed consent. PK, safety, and immunogenicity assessments were conducted for 70 days. PK similarity for a given test-to-reference comparison was considered to be demonstrated if the 90% CI of the test-to-reference ratio of the AUC from time 0 to the last time point (AUCT) and maximum concentration (Cmax) were within 80% – 125%. Results: The baseline demographics for the 101 subjects evaluable for PK were similar among 3 treatment arms. The 3 study drugs exhibited similar characteristics of target-mediated disposition and similar PK parameters (Table). The 90% CI for the ratios of Cmax, AUCT, and AUC0-∞were within 80% – 125% for the comparisons of PF-05280014 to trastuzumab-EU or trastuzumab-US, and trastuzumab-EU to trastuzumab-US. Adverse events (AE) were similar for the 3 arms with treatment-related AEs reported by 71.4%, 68.6%, and 65.7% subjects in the PF-05280014, trastuzumab-EU and trastuzumab-US, respectively. No serious AEs were reported. Only 4 subjects had treatment interruptions; 2 discontinued. Only 1 subject (trastuzumab-EU) developed anti-drug antibodies after dosing. Conclusions: This study demonstrates PK similarity of PF-05280014 to both trastuzumab-US and trastuzumab-EU and of trastuzumab-EU to trastuzumab-US. The three study drugs also showed similar safety profiles. Clinical trial information: NCT01603264.

Mean (±SD) PK exposure estimates.
Parameters (units) PF-05280014 Trastuzumab-EU Trastuzumab-US
N 34 35 32
Cmax (μg/mL) 159 ± 26 174 ± 31 164 ± 31
AUCT (μg·hr/mL) 35700 ± 6287 38510 ± 6569 35870 ± 6878
AUC0-∞ (μg·hr/mL) 37130 ± 6305 40330 ± 6994 37310 ± 6728