Hans-Christian Kolberg, MD
Trastuzumab (Herceptin) has proven to be a go-to target in the development of biosimilars. MYL-1401O (Ogivri; trastuzumab-dkst) was approved by the FDA in December 2017, and agents such as SB3 and ABP 980 have shown similar pathologic complete response (pCR) rates to the originator biologic.
In results from the phase III LILAC study presented at the 2018 ASCO Annual Meeting, ABP 980 showed a pCR equivalent to that of trastuzumab. This was the first study of a biosimilar in neoadjuvant breast cancer to include a central pathology review, as well as instances of switching patients from trastuzumab to ABP 980, according to lead author Hans-Christian Kolberg, MD.
The FDA issued Amgen, the developer of ABP 980, a complete response letter for the biosimilar in May 2018. However, Kolberg said that investigators are dedicated to working with the FDA to bring the biosimilar to the United States. Additionally, the European Medicines Agency’s Committee for Medicinal Products for Human Use has adopted a positive opinion for the marketing authorization of ABP 980.
In an interview with OncLive®
during the 2018 ASCO Annual Meeting, Kolberg, head, Department of Obstetrics and Gynecology, Breast Cancer Center, and Gynecologic Cancer Center at Marienhospital Bottrop, Klinik für Gynäkologie und Geburtshilfe, Bottrop, Germany, discussed ABP 980 and the future of biosimilars in oncology.
OncLive: Can you provide some background on this study?
: The LILAC study was the registrational study for ABP 980, a biosimilar for the monoclonal antibody trastuzumab, which is used in HER2-positive breast cancer. In HER2-positive breast cancer, it is used in the early and metastatic stages. Trastuzumab is also approved for [patients with] HER2-positive gastric cancer.
This study was in neoadjuvant breast cancer for HER2-positive patients who had tumors larger than 2 cm. These patients received chemotherapy, anthracycline, and taxane-containing chemotherapy in combination with either trastuzumab or ABP 980. After surgery, the group of patients receiving the originator trastuzumab was split again and randomized for a second time, because half of the patients received a biosimilar after receiving the originator in the adjuvant phase.
One thing that is important is that this is the first study of neoadjuvant breast cancer that included a central pathology review. This is always difficult because we are not only sending around biopsies, we had to send around specimens. This is the first time that a central pathologist decided if it was a pCR or not. We have centers all over the world, so there was a discussion of whether this was feasible or not. It did work; we had enough specimens brought to the central pathology. It was very important because in the end, the central pathology review showed the similarity of the biosimilar because the pCR ratios were in the predefined range. Whereas, in the local pathology, the results were so heterogeneous that we could not show the same results. It was very good that we included that before as a coprimary endpoint, and we met that endpoint.
Can you provide more detail on the journey that ABP 980 has taken so far?
ABP 980 is a biosimilar, and the approval process and study program for a biosimilar is different from a study program for a new biologic. You must first do pharmacokinetic and pharmacodynamic studies when developing a biosimilar. In this case, the first study was in healthy individuals, just to show it was safe and to show pharmacokinetic and pharmacodynamic data.
This is the first study showing clinical data on the biosimilar. That is because for the approval of a biosimilar, you do not need the process of phase I, II, and III studies. What you need is 1 phase III study with an efficacy endpoint. That is adding to this concept of totality of evidence that we are using in biosimilars.