P3-5-20PF-05280014, a potential biosimilar to trastuzumab: Overview and clinical development in Japan

Trastuzumab is approved in Japan for HER2-overexpressing breast cancer and is part of the standard-of-care treatment regimen in these patients. Biosimilars are developed such that there are no clinically meaningful differences between the biosimilar and reference product in terms of safety, purity, and potency. A trastuzumab biosimilar may enhance care by improving treatment access.PF-05280014 is being developed as a potential biosimilar to trastuzumab. Its development began with quality assessments followed by nonclinical studies that showed PF-05280014 and trastuzumab have similar structural, analytical, and functional characteristics. A phase 1, double-blind study (NCT01603264) in 105 healthy male volunteers showed pharmacokinetic (PK) similarity between PF-05280014 and trastuzumab marketed in the EU (trastuzumab-EU) and US (trastuzumab-US) and between trastuzumab-EU and trastuzumab-US, with 90% confidence intervals of Cmax, AUCT, and AUC0-infinity within 80.00%-125.00% for each comparison (Yin et al. Br J Clin Pharm 2014). Adverse event rates were similar between groups; all subjects, except one in the trastuzumab-EU group, were anti-drug antibody negative.An ongoing phase 3, randomized, double-blind study (NCT01989676) compares PF-05280014 + paclitaxel with trastuzumab + paclitaxel for first-line treatment of HER2-positive metastatic breast cancer. The primary objective is to compare the objective response rate between arms. Secondary objectives include evaluation of safety, secondary tumor control measures, population PK, and immunogenicity. This study is planned to enroll 690 female patients from sites worldwide, including Japan. Another phase 3, randomized, double-blind study (NCT02187744) using PF-05280014 in the neoadjuvant setting is ongoing.Positive results from studies of PF-05280014 conducted thus far support its development as a potential biosimilar to trastuzumab.Funding: Supported by Pfizer Inc. Trastuzumab is approved in Japan for HER2-overexpressing breast cancer and is part of the standard-of-care treatment regimen in these patients. Biosimilars are developed such that there are no clinically meaningful differences between the biosimilar and reference product in terms of safety, purity, and potency. A trastuzumab biosimilar may enhance care by improving treatment access. PF-05280014 is being developed as a potential biosimilar to trastuzumab. Its development began with quality assessments followed by nonclinical studies that showed PF-05280014 and trastuzumab have similar structural, analytical, and functional characteristics. A phase 1, double-blind study (NCT01603264) in 105 healthy male volunteers showed pharmacokinetic (PK) similarity between PF-05280014 and trastuzumab marketed in the EU (trastuzumab-EU) and US (trastuzumab-US) and between trastuzumab-EU and trastuzumab-US, with 90% confidence intervals of Cmax, AUCT, and AUC0-infinity within 80.00%-125.00% for each comparison (Yin et al. Br J Clin Pharm 2014). Adverse event rates were similar between groups; all subjects, except one in the trastuzumab-EU group, were anti-drug antibody negative. An ongoing phase 3, randomized, double-blind study (NCT01989676) compares PF-05280014 + paclitaxel with trastuzumab + paclitaxel for first-line treatment of HER2-positive metastatic breast cancer. The primary objective is to compare the objective response rate between arms. Secondary objectives include evaluation of safety, secondary tumor control measures, population PK, and immunogenicity. This study is planned to enroll 690 female patients from sites worldwide, including Japan. Another phase 3, randomized, double-blind study (NCT02187744) using PF-05280014 in the neoadjuvant setting is ongoing. Positive results from studies of PF-05280014 conducted thus far support its development as a potential biosimilar to trastuzumab. Funding: Supported by Pfizer Inc.