Shanghai Henlius Biotech, Inc. announced that the investigational new drug application (IND) for a phase 2 clinical trial of HANSIZHUANG (serplulimab), an innovative anti-PD-1 monoclonal antibody (mAb) independently developed by the Company, in combination with HANBEITAI (bevacizumab biosimilar) and HLX07 (innovative anti-EGFR mAb) for the first-line treatment of unresectable or metastatic hepatocellular carcinoma (HCC) has been approved by the National Medical Products Administration (NMPA). Previously, 9 immuno-oncology trials have been conducted on serplulimab.
Liver cancer is a common malignant tumor around the world, and it is the fourth most common cancer and the second cause of cancer death in China, seriously threatening the life and health of Chinese people. Most liver cancer patients are diagnosed at an advanced stage and lack the opportunity for radical surgery, resulting in a poor prognosis. Hepatocellular Carcinoma (HCC) is the most common type of liver cancer, accounting for 70% to 90% among liver cancer. The first-line therapy for patients with advanced unresectable liver cancer in China includes molecular targeted therapy, anti-PD-1/L1 mAb combined with bevacizumab, etc.. The emergence of immunotherapy has prolonged the survival time of patients with liver cancer. However, we still face many difficulties in the treatment of liver cancer, and more effective therapeutics need to be explored.
Henlius has conducted several clinial trials on serplulimab combined with either HANBEITAI or HLX07. The preliminary results of Phase 2 clinical study of serplulimab combined with HANBEITAI in the first-line treatment of unresectable or metastatic advanced HCC have been obtained, with a favorable efficacy and safety. And the related study has been published in 2021 CSCO. In addition, preclinical studies of HLX07 have shown that it can significantly inhibit the growth of tumor cells in different tumor models and has synergistic effect with serplulimab. Also, the Phase 2 study of serplulimab in combination with HLX07 has stated a good preliminary efficacy in head and neck squamous cell carcinoma (HNSCC). It is believed that serplulimab combined with HLX07 and HANBEITAI in HCC clinical trial will provide a new regimen for first-line treatment of HCC.
HANSIZHUANG (serplulimab) is the first innovative mAb developed by Henlius. It has been approved by the NMPA for the treatment of Microsatellite Instability-High (MSI-H) solid tumors. Henlius actively promotes HANSIZHUANG in conjunction with in-house products of the company such as tumor-specific target, angiogenesis target, immunotherapeutic target, etc. and chemotherapy drugs to conduct immune combination therapies in a wide variety of indications, such as lung cancer, HCC, esophageal carcinoma, head and neck squamous cell carcinoma and gastric cancer, etc. In the first-line treatment of lung cancer, the NDAs of the treatment for squamous non-small cell lung cancer (sqNSCLC) and extensive-stage small cell lung cancer (ES-SCLC) have been accepted by the NMPA. Henlius also plans to file MAA on ES-SCLC in the EU in 2022. There’s no PD-1 has been approved globally for first-line treatment of SCLC up to date, and HANSIZHUANG would potentially be the world’s first PD-1 inhibitor for the first-line treatment of SCLC.
Going forward, Henlius will continue conducting clinical studies for more innovative products in bispecific antibodies and the antibody-drug conjugates (ADC) and exploring combination therapies with improved efficacy to provide patients with quality and affordable biologics.
HANSIZHUANG (recombinant humanized anti-PD-1 monoclonal antibody injection, generic name: serplulimab injection) is the first innovative monoclonal antibody developed by Henlius. It is approved by the NMPA for the treatment of MSI-H solid tumors in March 2022. Henlius actively promotes HANSIZHUANG in conjunction with in-house products of the company and innovative therapies. It has successively obtained clinical trial licenses in China, the United States, the European Union and other countries and regions to initiate 9 clinical trials on immuno-oncology combination therapies of HANSIZHUANG worldwide in a wide variety of indications, such as lung cancer, esophageal carcinoma, head and neck squamous cell carcinoma and gastric cancer, etc., and covering the full range of first-line treatments of lung cancers. Up to date, the company has enrolled more than 2,800 subjects in China, Turkey, Poland, Georgia and other countries and regions, and the proportion of Caucasian is over 30% in two MRCTs, making HANSIZHUANG an anti-PD-1 mAb with one of the largest global clinical data pools. The NDA of the treatment for squamous non-small cell lung cancer (sqNSCLC) has been accepted by the NMPA and is expected to be approved in 2022. Furthermore, the global multi-center phase 3 clinical study of HANSIZHUANG in combination with chemotherapy in previously untreated extensive small-cell lung cancer (ES-SCLC) met the primary endpoint of overall survival (OS) with remarkable readouts. Its NDA in China has been accepted by the NMPA and MAA in the EU are expected to be filed in 2022, making this product potentially the world’s first anti-PD-1 mAb for the first-line treatment of SCLC.
HANBEITAI, a bevacizumab biosimilar developed and manufactured by Henlius independently, has been approved by the National Medical Products Administration (NMPA). It is indicated for the treatment of metastatic colorectal cancer (mCRC) and unresectable, locally advanced, recurrent or metastatic non-squamous non-small cell lung cancer (nsNSCLC). The Phase 3 study of HANBEITAI was published at the 23rd annual conference of Chinese Society of Clinical Oncology (CSCO) for the first time and awarded an “outstanding study paper”. And then the Phase 3 results were published on the world-renowned journal BioDrugs. The Phase 1 clinical study results were also published on Cancer Chemotherapy and Pharmacology.
HLX07, a humanised anti-EGFR mAb, is a bio-better independently developed by Henlius. Adopting the self-developed advanced antibody engineering platform, Henlius re-engineered cetuximab by humanizing its Fab regions and minimizing its glycan contents to generate HLX07 to reduce the immunogenicity and increase its affinity. Pre-clinical studies have shown that HLX07 binds to EGFR with similar affinity and favorable safety profile and has better bioactivity compared to cetuximab. HLX07 can significantly inhibit the growth in different tumour models and synergize with immune checkpoint inhibitors such as serplulimab. The company is proposing to commence more Phase 2 clinical trial of serplulimab combined with HLX07 on other tumours in the near future.
 Rongshou Zheng, Siwei Zhang, Hongmei Zeng, et al. Cancer incidence and mortality in China, 2016[J]. Journal of the National Cancer Center,2022, DOI: 10.1016/j.jncc.2022.02.002.
 Guidelines for the diagnosis and treatment of primary liver cancer ( 2022 edition) .
 Tseng,Yun-Chih Cheng, Chieh-Hsin Ho, Shih Chieh Chen, Yanling Wang, Eugene Liu, Hassan Issafras & Weidong Jiang (2021) Distinguishing features of a novelhumanized anti-EGFR monoclonal antibody based on cetuximab with superiorantitumor efficacy, Expert Opinion on Biological Therapy, 21:11, 1491-1507.