New Data Reported for Trastuzumab Biosimilars CT-P6 and HLX02 at ESMO 2019

Biosimilar trastuzumab is becoming a feature of the biosimilar landscape in both Europe and the United States, with 5 agents (Herzuma, Kanjinti, Ontuzant, Ogivri, and Trazimera) approved in both territories and with additional biosimilars in the drugmakers’ pipelines. During the European Society for Medical Oncology (ESMO) Congress 2019, held in Barcelona, Spain from September 27 to October 1, researchers reported new data from phase 3 studies of 2 such biosimilar products.

CT-P6 and reference trastuzumab are similar in DFS and OS up to year 3

Celltrion’s biosimilar trastuzumab, CT-P6, approved as Herzuma, has been the subject of numerous studies, including a phase 3 study in patients receiving neoadjuvant treatment for HER2-positive early breast cancer. Additionally, researchers recently reported results form a post hoc subgroup analysis from the adjuvant period of treatment; these results, say the authors, demonstrate that the biosimilar, used in the adjuvant setting, has comparable efficacy and safety to the reference at 1 year.

During ESMO 2019, researchers presented 3-year follow-up data, and conclude that the rates of disease-free survival (DFS) and overall survival (OS) at a median of 39 months support the similarity of the biosimilar and its reference in patients with early breast cancer (EBC).¹

In the phase 3 study, results of which have been published elsewhere, 549 patients with HER2-positive EBC were randomized to receive the biosimilar (n = 271) or its reference (n = 278) with docetaxel for cycles 1 through 4 and 5-fluorouracil, epirubicin, and cyclophosphamide for cycles 5 to 8. After surgery, patients received their assigned trastuzumab as monotherapy for 1 year and were then followed up to year 3.

The investigators found that the number of DFS events in each treatment arm were comparable in the intent-to-treat set, with 42 (16.3%) DFS events in the CT-P6 group versus 36 (13.8%) in the reference group and 18 (6.6%) OS events in the biosimilar group versus 18 (6.5%) in the reference group. Median DFS and OS have not been reached due to an insufficient number of events, the investigators note.

In terms of cardiac safety, the mean left ventricular ejection fraction was greater than 60% in both groups, and no new cases of heart failure were reported during the follow-up period.

HLX02 shows equivalence to EU-licensed trastuzumab in phase 3 study

China-based drug maker Henlius is currently awaiting the European Medicines Agency’s decision on its marketing authorization application for a trastuzumab biosimilar, HLX02, referencing Herceptin.

The company’s application for the product relies on a data package that includes a demonstration of safety and pharmacokinetic equivalence of the biosimilar and its US- and EU-licensed reference products in 109 healthy volunteers, as well as a phase 3 study in 649 patients with breast cancer at 89 centers in China, Ukraine, Poland, and the Philippines.

During ESMO 2019, researchers reported on the findings of that phase 3 study, and said that the biosimilar and the EU-licensed reference resulted in equivalent overall response rates (ORR) at week 24.²

In the study, patients who had HER2-positive breast cancer, Eastern Cooperative Oncology Group performance status of 0 to 1, and estimated life expectancy 3 months or greater were randomized to receive either the biosimilar (n = 324) or the reference trastuzumab (n = 325) with docetaxel on day 1 of the first cycle of chemotherapy, followed by their assigned trastuzumab every 3 weeks up to 12 months. The primary end point was best ORR at week 24, and the prespecified equivalence margin was set at  ±13.5%.

At week 24, the ORR was 71.0% for the biosimilar group (95% CI, 66.0%-75.9%) and 71.4% for the reference group (95% CI, 66.5%-76.3%, P = .952), which fell within the equivalence margin. The difference in ORR was 0.4 (95% CI, —7.4 to 6.6). Additionally, safety and immunogenicity outcomes were similar, and no new safety signals were identified for the biosimilar.

The authors note that further results at month 12 will be reported in the future.

References

1. Stebbing J, et al. 3-year follow-up of a phase III trial comparing the efficacy and safety of neoadjuvant and adjuvant trastuzumab and its biosimilar CT-P6 in HER2 positive early breast cancer (EBC). Presented at: European Society for Medical Oncology Congress 2019; September 27 to October 1, 2019; Barcelona, Spain. Abstract 190P.

2. Xu B, et al. Efficacy and safety of first China-manufactured trastuzumab biosimilar HLX02 for metastatic breast cancer: A phase III trial. Presented at: European Society for Medical Oncology Congress 2019; September 27 to October 1, 2019; Barcelona, Spain. Abstract 309PD.