Amgen and Allergan have announced results from a phase 3 study evaluating efficacy and safety of ABP 980 compared with trastuzumab in patients with human epidermal growth factor receptor 2-positive (HER2-positive) early breast cancer.

The results ruled out inferiority compared to trastuzumab but could not rule out superiority based on its primary efficacy endpoint of the difference of the percentage of patients with a pathologic complete response (pCR). The primary endpoint had a prespecified equivalence margin of +/- 13 percent and the observed upper end of the confidence interval was 13.4 percent.

Overall, adverse events were comparable between ABP 980 and trastuzumab. In the neoadjuvant phase of the study, which included chemotherapy, there were more serious adverse events reported in the ABP 980 group, the majority of which were reported by the investigators as unlikely related to investigational product. In the adjuvant phase of the study, which did not include chemotherapy, serious adverse events were comparable between treatment groups. The overall results also showed comparable immunogenicity.

"We believe this study confirms no clinically meaningful differences between ABP 980 and trastuzumab, and we look forward to continued discussions with regulatory authorities," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "Biosimilars are approved based on the analytical, nonclinical and clinical data, and we believe that the totality of the evidence we've generated supports ABP 980 as highly similar to the reference product."

"These results provide significant clinical evidence that ABP 980 could be an important biosimilar treatment option for patients with HER2-positive early breast cancer," said David Nicholson, chief research and development officer, Allergan. "Allergan is committed to the continued development of ABP 980 and other biosimilars that provide safe, high-quality and effective therapies in key disease areas."

ABP 980 is being developed as a biosimilar to trastuzumab, a recombinant DNA-derived humanized monoclonal immunoglobulin G1 kappa antibody which targets HER2. Trastuzumab is approved in many regions for the treatment of HER2-positive early breast cancer, metastatic breast cancer and metastatic gastric cancer.

Amgen and Allergan are collaborating on the development and commercialization of four oncology biosimilars. Amgen has a total of nine biosimilars in development. Allergan is also independently developing biosimilars.

This above referenced phase 3 study was a randomized, multicenter, double-blinded, active-controlled study (study number 20120283) that evaluated safety and efficacy of ABP 980 compared to trastuzumab in adult female patients with HER2-positive early breast cancer. There were 725 patients randomized, with 364 patients in the ABP 980 group and 361 patients in the trastuzumab group.

In the neoadjuvant phase, enrolled patients received run-in chemotherapy consisting of epirubicin and cyclophosphamide (EC) every three weeks (Q3W) for four cycles. Once run-in chemotherapy was completed, patients with adequate cardiac function were randomized 1:1 to receive investigational product (ABP 980 or trastuzumab), plus paclitaxel, Q3W for four cycles. Surgery (breast and sentinel node or axillary lymph node resection) was complete three to seven weeks after the last dose of investigational product in the neoadjuvant phase, and pCR was analyzed.

In the adjuvant phase, following surgery, patients received investigational product (ABP 980 or trastuzumab) Q3W for up to one year from the first day of investigational product administered in the neoadjuvant phase. Patients who received ABP 980 during the neoadjuvant phase continued to receive ABP 980 Q3W for the adjuvant phase. Patients who received trastuzumab during the neoadjuvant phase received either ABP 980 or trastuzumab Q3W for the adjuvant phase. The allocation to a treatment group during the neoadjuvant or adjuvant phase occurred at randomization.

The primary analysis was conducted when the last patient completed the surgery following the neoadjuvant therapy. Clinical equivalence was assessed by comparing the confidence interval of the risk difference and risk ratio of the pCR in breast tissue and axillary lymph nodes with the prespecified equivalence margins. The final analysis of safety will be conducted when the last patient has completed their last study assessment in the adjuvant phase.

HER2-positive early breast cancer is a breast cancer that tests positive for a protein called human epidermal growth factor receptor 2 (HER2), which promotes the growth of cancer cells. Approximately 20 percent of all breast cancers are HER2-positive. Breast cancer is the second leading cause of cancer death among women and each year it is estimated that over 230,000 women in the United States will be diagnosed. HER2-positive breast cancers tend to grow and spread more aggressively than HER2-negative breast cancers.

ABP 980 is being developed as a biosimilar to trastuzumab, a recombinant DNA-derived humanized monoclonal immunoglobulin G1 kappa antibody approved in many regions for the treatment of HER2-overexpressing early breast cancer, metastatic breast cancer and metastatic gastric cancer. The active ingredient of ABP 980 is a humanized monoclonal antibody which has the same amino acid sequence as trastuzumab. ABP 980 has the same pharmaceutical dosage form and strength as trastuzumab (US) and trastuzumab (EU).