Abstract OT1-1-03: A phase 3 randomized, double-blind trial comparing PF-05280014 + paclitaxel vs. trastuzumab + paclitaxel for treatment of HER2+ metastatic breast cancer patients

Abstract

Abstract Background: PF05280014 is being developed as a potential biosimilar to trastuzumab. PF-05280014 demonstrated similarity to trastuzumab in nonclinical evaluations. In a Phase I trial in healthy volunteers, PF-05280014 pharmacokinetic characteristics and safety profile were shown to be similar to those of trastuzumab. The goal of this Phase 3 trial is to demonstrate that the efficacy and safety of PF-05280014 + paclitaxel are similar to those of trastuzumab sourced from the EU (trastuzumab-EU) + paclitaxel in women with HER2-positive metastatic breast cancer. Trial design: In this randomized, double-blind trial, patients will be randomized 1:1 into 2 arms: PF-05280014 + paclitaxel and trastuzumab-EU + paclitaxel. Randomization will be stratified by prior adjuvant trastuzumab exposure and estrogen receptor status. The order of infusion will be PF-05280014 or trastuzumab (4 mg/kg in Cycle 1; 2 mg/kg thereafter over 90 min) first followed by paclitaxel (80 mg/m2). Eligibility: Female patients, aged ≥18 y with confirmed HER-2 overexpressing metastatic breast cancer, ≥1measurable lesion (RECIST), Eastern Cooperative Oncology Group status 0–2, normal left ventricular ejection fraction, and normal laboratory values are eligible. Key exclusion criteria are prior systemic therapy for metastatic disease, prior cumulative dose of anthracyclines >400 mg/m2, and major surgery, radiotherapy or investigational agents within 4 weeks. All subjects must provide informed consent. Aims: The primary objective is to demonstrate the similarity in objective response rate (ORR) of PF-05280014 + paclitaxel treatment to that of trastuzumab-EU + paclitaxel. Secondary objectives include evaluating 1-year progression-free survival, safety, pharmacokinetics, and immunogenicity of these combination treatments. Statistical methods: This study tests whether the ORR of PF-05280014 is similar to that of trastuzumab-EU, using a margin of 13%, i.e., 5% alpha for non-inferiority. Assuming 60% ORR in both arms, 600 patients (300/arm) will be needed to achieve 90% power. Assuming 10% attrition, a total of 660 patients will be randomized. The intent-to-treat (ITT) population is defined as all subjects who are randomized to receive treatment. The per-protocol population is defined as all subjects who are randomized to and receive treatment and do not have any major protocol violations and will be used for evaluation efficacy endpoints. Accrual: The target accrual of this global trial is 660 patients. Contact information: For further information, please contact the Director, Clinical Trials Disclosure Group, Pfizer Inc. (marla.brickman@pfizer.com). Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr OT1-1-03.