A phase 1 trial of ABP 980, Amgen’s proposed biosimilar of reference trastuzumab (Herceptin), demonstrated ABP 980’s pharmacokinetic similarity to both US-approved reference trastuzumab and European Union-approved reference trastuzumab. Amgen and Allergan have submitted applications for approval of ABP 980 with both the FDA and the European Medicines Agency.
A phase 1 trial of ABP 980, Amgen’s proposed biosimilar of reference trastuzumab (Herceptin), demonstrated ABP 980’s pharmacokinetic (PK) similarity to both US-approved reference trastuzumab and European Union (EU)-approved reference trastuzumab, and no differences in safety and tolerability between treatments were noted.
Reference trastuzumab is approved as a treatment for metastatic breast cancer, early breast cancer, and metastatic gastric cancer, and is the standard of care for patients with human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer. Amgen and Allergan have submitted applications for approval of ABP 980 with both the FDA and the European Medicines Agency (EMA).
According to Vladimir Hanes, MD, and colleagues at Amgen, the study was conducted to meet FDA and European Medicines Agency guidelines for the development and approval of biosimilar agents. Their findings, published in Cancer Chemotherapy Pharmacology, support ABP 980’s similarity to trastuzumab by demonstrating its PK equivalence to both the US- and EU-approved products, the researchers said.
This single-blind study randomized 157 healthy males 1:1:1 to receive a single 6-mg/kg intravenous infusion of ABP 980, US trastuzumab, or EU trastuzumab. 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 and 90% confidence interval (CI) for Cmax and AUCinf had to be within the equivalence criteria of 0.80 to 1.25. The study found that these endpoints were met and that the tolerability and safety of ABP 980, US trastuzumab, and EU trastuzumab were comparable. No new or unexpected safety signals were noted, the researchers noted.
The study design also allowed for a direct comparison between US and EU trastuzumab: the data met the equivalence margin of 0.8 to 1.25 for US trastuzumab versus EU trastuzumab and established PK bioequivalence between the 2 products, thus allowing use of 1 reference product in future comparative phase 3 studies. The researchers also found the safety and tolerability of US and EU trastuzumab to be comparable.
None of the trial participants developed anti-drug antibodies (ADAs), a finding that is consistent with previous studies demonstrating a low incidence of ADAs with trastuzumab treatment. Overall, the incidence of treatment emergent adverse events (TEAEs) was similar across treatment groups, and the majority of TEAEs were mild to moderate in severity. The most frequently reported TEAEs were headache, upper respiratory tract infection, chills, pyrexia, myalgia, nausea, epistaxis, arthralgia, and lethargy. There were no deaths or TEAEs that led to study discontinuation.
“In conclusion, in this [phase 1] study, there were no differences between ABP 980, trastuzumab (US), and trastuzumab (EU) with respect to PK profile, safety, and tolerability after a single IV infusion,” the study’s authors state. “These results provide further support that the proposed biosimilar ABP 980 is highly similar to FDA-licensed and EU-authorized trastuzumab reference products.”