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Henlius Released Phase 3 Study Data of its Bevacizumab Biosimilar HLX04 at ESMO Asia 2020


The ESMO Asia Virtual Congress will be held from 20th to 22nd November 2020. At this congress, Henlius will release 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 principal investigators of this trial are Prof. Shukui Qin from Qinhuai Medical Treatment Area of General Hospital of Eastern Theater Command and Prof. Jin Li from Shanghai East Hospital, Tongji University.

Details of this study are as follows:

Title: Safety and Efficacy of HLX04 versus Reference Bevacizumab in Combination with XELOX or mFOLFOX6 as First-Line Treatment for Metastatic Colorectal Cancer: A Randomised, Double-blind Phase 3 Study

Form: E-poster

Poster number: 104P

Presenter: Shukui Qin, M.D. Ph.D., Qinhuai Medical Treatment Area of General Hospital of Eastern Theater Command

Time: 12:00 hrs GMT+8:00, 19th Nov. 2020 to 24:00 hrs GMT+8:00, 29th Nov. 2020

HLX04 is a bevacizumab biosimilar developed by Henlius independently in accordance withTechnical 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.

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 investigated in 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.

In addition, to explore the potential activity of VEGF inhibitors against ophthalmic diseases and for the benefit of more patients, Henlius is also developing HLX04 for the treatment of eye diseases including wet age-related macular degeneration (wAMD) and diabetic retinopathy(DR). The investigational new drug application has been approved by NMPA. Recently, Henlius has also entered into a co-development and exclusive license agreement with Essex Bio-Technology to co-develop HLX04 indicated for ophthalmic diseases such as wAMD, fully utilizing the advantages of Henlius in research and development and Essex in global commercialisation of ophthalmic drugs. As of now, Henlius has submitted a patent for a new formulation of HLX04 with potential better safety and stability, designed for ophthalmic use.

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 (7.5 mg/kg every 3 weeks when combined with XELOX or 5 mg/kg every 2 weeks when combined with mFOLFOX6). The primary endpoint was progression-free survival rate at week 36 (PFSR36wk).


· Efficacy-Primary endpoint

675 patients were enrolled (HLX04, N=338; Reference bevacizumab, N=337). Per FAS, PFSR36wk were 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.


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.