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First Patient Dosed in a Phase 1 Clinical Study of Henlius Novel Anti-GARP and Anti-PD-1 Dual mAb Therapy in Australia


Shanghai, China, Dec 14th, 2022 - Shanghai Henlius Biotech, Inc. (2696.HK) announced the first subject was dosed in Australia in a phase 1 clinical trial (HLX60HLX10-FIH101) of its independently developed HLX60 (recombinant anti-GARP humanised monoclonal antibody injection) in combination with HANSIZHUANG, an innovative anti-PD-1 mAb independently developed by the company for the treatment of advanced or metastatic solid tumours. HLX60 is the first anti-GARP monoclonal antibody (mAb) that has been approved to conduct clinical studies in China. Recently, the first subject has been dosed for phase 1 clinical trial of HLX60 in China.

Immune checkpoint inhibitor (ICI) therapies have offered a novel way to attack tumour cells in recent years. Current research on immune checkpoint inhibitors is mainly focused on anti-CTLA-4 (cytotoxic T lymphocyte associated antigen-4) antibody, anti-PD-1 (programmed cell death protein 1) antibody, and anti-PD-L1 (programmed cell death-ligand 1) antibody. PD-1/PD-L1 plays a vital role in immune suppression and have been approved for treating several indications including melanoma, non-small cell lung cancer, hepatocellular carcinoma, and classical Hodgkin lymphoma. However, only 30-40% of patients benefit from the treatment of immune checkpoint inhibitors and their tumours still recur or progress. Some cancer species still lack response to ICIs [1-2]. Therefore, there is an urgent need to develop new therapies to meet the huge medical needs.


Transforming growth factor-β (TGF-β) is a pleiotropic cytokine expressed by the majority of cells and found in many tissues. There are three TGF-β receptor ligands: TGF-β1, TGF-β2, and TGF-β3, with TGF-β1 playing critical roles in a variety of biological processes including cell proliferation, development, apoptosis, fibrosis, angiogenesis, wound healing, cancer, and many others [3–5]. The glycoprotein-A repetitions predominant (GARP) is highly expressed on the surface of activated Tregs and platelets and acts as a docking receptor by binding to latent transforming growth factor-β1 (LTGF-β1) [6]. It concentrates LTGF-β1 on the cell surface and releases active TGF-β1 in the tumour microenvironment (TME), thus inhibiting anti-tumour immune response and inducing tumour cell growth, proliferation and invasion [7-8].


HLX60 is a self-developed novel anti-GARP mAb that binds to GARP and specifically blocks the release of GARP mediated TGF-β1, thus relieving the immunosuppression caused by TGF-β1, reversing the immunosuppressive TME, and improving anti-tumour immune response. Furthermore, by inducing antibody dependent cell-mediated cytotoxicity (ADCC) effect, HLX60 can deplete GARP positive tumour cells as well as immunosuppressive cells such as Tregs. Several pre-clinical studies have shown that combining HLX60 and HANSIZHUANG has a synergistic effect in inhibiting tumour growth and has good tolerance and safety. These findings suggested that the combination therapy of HLX60 and HANSIZHUANG is superior to either HANSIZHUANG or HLX60 monotherapy.


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 NCT05483530

This phase 1 study aims to evaluate the safety, tolerability, and preliminary efficacy of HLX60 plus serplulimab in patients with advanced or metastatic solid tumours. The study will follow an accelerated titration design (ATD) in combination with “3+3” design. Eligible subjects will be given different doses of HLX60 as monotherapy (Q3W: 0.5, 2, 5, 15, and 25 mg/kg) intravenously in cycle 1, and then combined with serplulimab (Q3W: 300 mg) starting from cycle 2. The primary endpoints of this study are the dose-limiting toxicities (DLT) assessed within 3 weeks after the first dose of HLX60, as well as the maximum tolerated dose (MTD) of HLX60 and recommended phase 2 dose (RP2D) of HLX60 plus serplulimab. Secondary endpoints include safety, pharmacokinetic parameters, pharmacodynamic characteristics, immunogenicity, and efficacy.


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[7] Edwards JP, Thornton AM, Shevach EM. Release of active TGF-beta1 from the latent TGF-beta1/GARP complex on T regulatory cells is mediated by integrin beta8. J Immunol. 2014;193(6):2843–9.

[8] Stockis J, Lienart S, etc. Blocking immunosuppression by human Tregs in vivo with antibodies targeting integrin alphaVbeta8. Proc Natl Acad Sci U S A. 2017;