Shanghai, China, August 15th, 2022 - Shanghai Henlius Biotech, Inc. (2696.HK) announced that the first subject doesd for a phase 1 clinical trial (NCT05400265) of HANSIZHUANG (serplulimab), an innovative anti-PD-1 monoclonal antibody (mAb) independently developed by the company, in combination with HLX26, an innovative anti-LAG-3 mAb, for the treatment of advanced/metastatic solid tumours. To date, there is no anti-PD-1 mAb and anti-LAG-3 mAb combination therapy approved in China. The combination therapy of dual immune checkpoint inhibitors is expected to bring new treatment for patients with solid tumours in China.
HLX26 is a human mAb targeting LAG-3 extracellular domains, which developed independently by Henlius. The first subject has been dosed with HLX26 for the phase 1 clinical trial in patients with advanced/metastatic solid tumours or lymphomas. LAG-3 (lymphocyte-activation gene 3) is an immune checkpoint receptor and a new generation of immunotherapy target after PD-1/L1 and CTLA-4. LAG-3 is mainly expressed on human immune cells, including activated T cells and part of NK cells, and negatively regulates T cells' proliferation, activation, and homeostasis[1-2]. Clinical studies have shown that LAG-3 inhibitors are effective against lung cancer, breast cancer, melanoma, head and neck cancer, hematological malignancy and so on. HLX26 can block the LAG-3-mediated signaling pathway to restore the killing function of T-cell. Pre-clinical studies proved that HLX26 has the anti-tumour effect and favorable tolerability and safety. Furthermore, in vitro and animal studies showed that HLX26 in combination with serplulimab have a significant synergistic effect in anti-tumour. These results lay the foundation for further clinical studies on combination usage. In April 2022, the investigational new drug application for phase 1 clinical trial of HANSIZHUANG in combination with HLX26 for the treatment of advanced/metastatic solid tumours or lymphomas has been approved by the National Medical Products Administration.
Underpinned by the patient-centric strategy, Henlius has achieved an overall layout of the immune checkpoint products of PD-1/L1, CTLA-4, LAG-3, etc., proactively exploring immuno-oncology combination therapy. Meanwhile, Henlius actively promotes HANSIZHUANG in conjunction with in-house products of the company such as tumour-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, esophageal carcinoma, head and neck squamous cell carcinoma and gastric cancer, etc., committing to bringing affordable and high-quality innovative biologics to patients around the world.
About NCT05400265
This open-label, dose-escalation, phase 1 study aims to evaluate the safety, tolerability, pharmacokinetic characteristics, and preliminary efficacy of HLX26 in combination with serplulimab in patients with advanced/metastatic solid tumours. Eligible patients were given different doses of HLX26 and fixed-dose serplulimab intravenously every 3 weeks following 3+3 dose-escalation design. The primary endpoints of this study are the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) determined within three weeks after the initial dose. Secondary endpoints include adverse events, pharmacokinetic parameters, immunogenicity, and preliminary efficacy.
About Serplulimab
HANSIZHUANG (recombinant humanized anti-PD-1 monoclonal antibody injection, generic name: serplulimab injection) is the first innovative monoclonal antibody developed by Henlius. Up to date, 1 indication is approved for marketing in China, 2 NDAs have been accepted by the NMPA, and 11 clinical trials are ongoing across the world.
HANSIZHUANG was approved by the NMPA for the treatment of MSI-H solid tumors in March 2022 and actively promotes its synergy 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 11 clinical trials on immuno-oncology combination therapies 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. As of now, 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 NDAs of the treatment for squamous non-small cell lung cancer (sqNSCLC) and the first-line treatment of extensive small-cell lung cancer (ES-SCLC) have been accepted by the NMPA, which makes HANSIZHUANG potentially the world’s first anti-PD-1 mAb for the first-line treatment of SCLC. Furthermore, HANSIZHUANG was recommended by the 2022 CSCO Guidelines for Diagnosis and Treatment of Small Cell Lung Cancer (SCLC) for the treatment of ES-SCLC and was also granted orphan drug designation by the FDA for treatment of SCLC. In the field of esophageal squamous cell carcinoma, the phase 3 clinical trial of HANSIZHUANG in combination with chemotherapy has met the co-primary endpoints.
Reference
[1] Ruffo E, Wu R C, Bruno T C, et al. Lymphocyte-activation gene 3 (LAG3): the next immune checkpoint receptor[C] //Seminars in immunology. Academic Press, 2019, 42: 101305.
[2] Solinas C, Migliori E, De Silva P, et al. LAG3: the biological processes that motivate targeting this immune checkpoint molecule in human cancer[J]. Cancers, 2019, 11(8): 1213.