HLX02, a China-manufactured Trastuzumab biosimilar, was independently developed by Shanghai Henlius Biotech, Inc. The clinical program followed the biosimilar guideline of China National Medical Products Administration (NMPA) and European Medicines Agency (EMA), which aims to increase global patient accessibility. We have reported the establishment of clinical PK bioequivalence between HLX02 and reference Trastuzumabs(CN and EU-sourced) at the annual meeting of CSCO and ESMO-Asia in 2018. The comparable Phase 3 study (HLX02-BC01, NCT03084237 and EudraCT: 2016-000206-10) is a randomized,double-blind, parallel-controlled trial in patients with untreated relapsed or metastatic HER2+breast cancer to demonstrate the equivalence in safety and efficacy between HLX02 and reference Trastuzumab (EU-sourced). We presented the Phase 3 results with partial sub-group analysis in CSCO, 2019 and different set of data in ESMO, 2019. Here in the 2019 ESMO-Asia congress, we announced the Week 24 efficacy result and the updated safety profile of this Phase 3 study.

The HLX02 Phase 3 study was chosen by ESMO-Asia congress as an oral presentation at Hall 405, the Suntec Singapore Convention & Exhibition Centre on 23rd Nov 2019. Among a number of accepted abstracts under the topic of breast cancer,our study is one of the five major studies selected by the committee for oral presentation and discussion. The section was chaired by professor R. Dent from the National Cancer Center in Singapore. Many experts excited about the positive results of this biosimilar study and held expectation for HLX02 to increase patient accessibility.

Study Design

The Phase 3 study(HLX02-BC01, NCT03084237 and EudraCT: 2016-000206-10) of HLX02 is a randomized,double-blind, parallel-controlled trial to demonstrate the equivalence in safety and efficacy between HLX02 and reference Trastuzumab sourced from European Union (EU- Trastuzumab). This Phase 3 study recruited subjects with previously-untreated relapsed or metastatic HER2+breast cancer from 89 centers in China, the Philippines, Poland and Ukraine. The key inclusion criteria included: adult female (age≥18); histologically confirmed HER2+ (FISH ≥2.0, or IHC >3) relapsed ormetastatic breast cancer; had not yet received systemic chemotherapy or anytargeted therapy; ECOG score from 0 to 1. Eligible subjects were randomized ina 1:1 ratio to receive either HLX02 or EU-Trastuzumab with docetaxel in 3-weekly cycles for up to 1 year. Primary endpoint was best overall responserate at Week 24 (ORR24w) after 8 treatment cycles.

Results(Data Cut-off Date: 27th Nov 2018)

Efficacy-Primary Endpoint

As data cutoff date of 27-November-2018，649 patients were randomized into two treatment groups(HLX02=324;EU-Trastuzumab =325).ORR24w was71.0% in HLX02 group and 71.4% in EU-Trastuzumab group  with no statistical difference observed between the two treatment groups. The risk differencein ORR24w between two groups was -0.4%. The 95% confidence interval of the difference (-7.4%,6.6%) was within the pre-defined margin (-13.5%, +13.5%),demonstrated the efficacy equivalence between HLX02 and EU-Trastuzumab. Sub-group analysis showed (Asianvs. non-Asian, and Chinese vs. non-Chinese) similar results (p>0.05), which further concluded the therapeutic equivalence.

Efficacy-Secondary Endpoints

Secondary endpoints including clinical benefit rate (CBR), disease control rate (DCR), duration of response (DoR),progression-free survival (PFS) and overall survival (OS) had no significant difference between two treatment groups (p>0.05).

Safety

The safety profiles, including the incidence of drug-related cardiac disorders, were also similar between HLX02 and EU-Trastuzumab (p>0.05).

Conclusion

HLX02 and EU-Trastuzumab demonstrated efficacy equivalence with 95% confidence interval of difference in ORR24w fell entirely within the pre-specified margin. Based on the available data by the data cutoff date, all secondary efficacy and safety analysis of HLX02 supported the conclusion of biosimilarity between HLX02 and EU-Trastuzumab in patients with previously-untreated relapsed or metastatic HER2+ breast cancer.