The 23rd annual meeting of Chinese Society of Clinical Oncology （CSCO） is held from 19th to 26th September 2020. At this meeting, Henlius for the first time released the Phase 3 study results of its bevacizumab biosimilar HLX04 (recombinant humanised anti-VEGF monoclonal antibody injection), which was developed by the company independently. The HLX04 Phase 3 study was awarded as outstanding study paper, and the study results were reported by Co-principal investigator of this trial, Professor Jin Li of Tongji University Shanghai East Hospital in an oral presentation in outstanding paper section of the conference plenary session on the first day of the conference.

Details of this study are as follows:

Title: HLX04, A Bevacizumab Biosimilar, Versus Reference Bevacizumab in Combination with XELOX or mFOLFOX6 as First-line Treatment for Metastatic Colorectal Cancer: A Phase 3 study

Form: Oral presentation

Presenter: Prof. Jin Li, Tongji University Shanghai East Hospital

Time: 11:05-11:20, 19th Sept. 2020

Place: 1st Floor of Meeting Hall, China World Hotel, Beijing

HLX04 is a bevacizumab biosimilar developed by Henlius independently in accordance with Technical Guidelines for the Development and Evaluation of Biosimilars (Tentative). The New Drug Application (NDA) of HLX04 has been accepted by the National Medical Products Administration (NMPA). Potential indications of HLX04 include advanced, metastatic or recurrent non-small cell lung cancer and metastatic colorectal cancer. Different from currently approved bevacizumab biosimilars in China, the Phase 3 study of HLX04 was conducted among Chinese patients with metastatic colorectal cancer, which helps to accumulate more clinical evidence and experience of bevacizumab in this patient population. In addition, to explore the potential of VEGF inhibitors for ophthalmic diseases, Henlius is also developing HLX04 for the treatment of eye diseases including wet age-related macular degeneration and diabetic retinopathy.

The Phase 3 clinical study data also laid the foundation for the development of the immune combination therapy of HLX04 and Henlius’ anti-PD-1 monoclonal antibody HLX10. Of note is that HLX04 plus HLX10 is the first domestic dual monoclonal antibody (mAb) combo therapy that has received Investigational New Drug Application approval from NMPA. This combination therapy is currently being developed for various solid tumours such as non-squamous non-small cell lung cancer and hepatocellular carcinoma. Clinical development of this combination therapy in first-line non-squamous non-small cell lung cancer patients has entered pivotal Phase 3 stage.

 Study design

HLX04-mCRC03 is a multi-centre, randomised, double-blind, parallel-controlled Phase 3 study (NCT03511963) aimed to compare the efficacy, safety and immunogenicity of HLX04 to reference bevacizumab in combination with chemotherapy (XELOX or mFOLFOX6) as first-line treatment in patients with metastatic colorectal cancer (mCRC). Enrolled patients were randomised (1:1) to receive either HLX04 or reference bevacizumab intravenously (7.5mg/kg every 3 weeks when combined with XELOX or 5mg/kg every 2 weeks when combined with mFOLFOX6). The primary endpoint was progression-free survival rate at week 36 (PFSR36wk).

Results

Efficacy-Primary endpoint

675 patients were enrolled (HLX04, N=338; Reference bevacizumab, N=337). Per FAS, PFSR36wk was 46.4% in HLX04 group and 50.7% in reference bevacizumab group. The group difference was -4.2% (90% CI: -10.6%, 2.1%), which fell entirely in the pre-defined equivalence margins (-11%, 15%), demonstrating equivalent efficacy between HLX04 and reference bevacizumab.

Efficacy-Secondary endpoints

There was no statistically significant difference (p >0.05) between the treatment groups in secondary endpoints, including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), time to response (TTR) and duration of response (DoR).

Safety and immunogenicity

The safety and immunogenicity profiles were similar between HLX04 and reference bevacizumab.

Conclusion

The results of the Phase 3 study demonstrated the equivalence in efficacy between HLX04 and reference bevacizumab with similar safety and immunogenicity profiles as first-line treatment for mCRC patients. HLX04 will provide an alternative treatment option for cancer patients as a potential biosimilar candidate.

About Henlius

Henlius (2696.HK) is a global biopharmaceutical company with the vision to offer high-quality, affordable and innovative biologic medicines for patients worldwide with a focus on oncology and autoimmune diseases. Since its inception in 2010, Henlius has built an integrated biopharmaceutical platform with core capabilities of high-efficiency and innovation embedded throughout the whole product life cycle including R&D, manufacturing and commercialisation. It has three R&D facilities in Shanghai, Taipei and California and a Shanghai-based manufacturing facility certificated by China and the European Union (EU) Good Manufacturing Practice (GMP).

Henlius has pro-actively built a diversified and high-quality product pipeline covering over 20 innovative monocolonal antibodies (mAb) and has continued to explore immuno-oncology combination therapies with proprietary HLX10 (anti-PD-1 mAb) as backbone. After 汉利康^® (HLX01, rituximab) was launched commercially, 汉曲优^® (HLX02, trastuzumab, EU brand name: Zercepac^®) also has been approved in the EU and China, becoming the first China-developed mAb biosimilar approved both in the EU and China. Up to date, in addition to 2 products launched successfully and 1 product (HLX03 adalimumab) to be potentially launched within 2020, Henlius has conducted over 20 clinical studies for 10 products and 8 combination therapies worldwide. Products have been licensed out to nearly 100 countries and regions.