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IND Application for the Clinical Trial of Novel Anti-TIGIT Fc Fusion Protein HLX53 in Combination with HANSIZHUANG Plus HANBEITAI for the First-Line Treatment of Locally Advanced or Metastatic Hepatocellular Carcinoma Patients Approved by NMPA


Shanghai, China, April, 17th, 2024 - Shanghai Henlius Biotech, Inc. (2696.HK) announced that the investigational new drug application (IND) for the clinical trial of HLX53, an anti-TIGIT Fc fusion protein, in combination with HANSIZHUANG (serplulimab, HLX10) and HANBEITAI (bevacizumab, HLX04) for the first line treatment of locally advanced or metastatic hepatocellular carcinoma, has been approved by the National Medical Products Administration (NMPA). A phase 2 clinical trial will be initiated to evaluate the safety, tolerance and efficacy of the multiple immunotherapy-based treatment combinations in patients with advanced or metastatic hepatocellular carcinoma.

Liver cancer is one of the most prevalent malignancy in the world. According to GLOBALCAN 2022, there are about 870,000 new cases diagnosed and 760,000 deaths for the tumour in the globe[1]. Meanwhile, primary liver cancer (PLC) is the fourth most common cause and the second mortality cancer in China, with about 370,000 new cases and 320,000 deaths in 2022[2]. From which, hepatocellular carcinoma (HCC) is the predominant pathological type of PLC, which accounts for between 85% and 90% of liver cancer cases[3]. Due to its insidious onset, lack of symptom in its early stage, and quick progression, PLC usually has been in its locally advanced stage or develops distant metastasis when it is diagnosed. As a result, the management becomes extremely difficult and the prognosis usually is poor. The 5-year survival rate of PLC is only about 18%[4]. For patients with advanced liver cancer, the first-line treatment is based on targeted therapy and immunotherapy. And the standard therapy (combination therapies of immune inhibitor plus anti-angiogenic treatment) have shown significant clinical anti-tumour efficacy and survival benefit[5]. However, some patients failed to benefit from the standard therapy and suffered from recurrence or progression of the disease. Thers is still an urgent clinical need to further expand the benefit population with advanced liver cancer and improve the efficacy of immunotherapy.

T-cell immunoglobulin and ITIM domains (TIGIT) has emerged as popular inhibitory checkpoint receptor, which is mainly expressed on natural killer (NK) cells, activated CD8+ T and CD4+ T cells, and T regulatory cells. TIGIT binds to the ligand CD155 (poliovirus receptor, PVR)[6-7], mainly expressed on antigen-presenting cells (APC) or the surface of tumour cells, to down-regulate T cell and NK cell functions1-2. As an immune checkpoint protein, TIGIT can inhibit innate and adaptive responses in various mechanisms of action and act as “brakes” like PD-1/PD-L1 does to stop T cells from attacking  tumours[8]. Studies have shown that TIGIT inhibitor are effective against lung cancer, gastric cancer, melanoma, multiple myeloma, etc[9]. Moreover, TIGIT has shown a synergistic effect with the PD-1 pathway in preclinical studies, indicating that simultaneous blocking of TIGIT and PD-1/PD-L1 signaling pathways is superior to blocking either pathway alone, which can enhance anti-tumour activity[10].

HLX53 is an anti-TIGIT Fc fusion protein independently developed by Henlius, consisting of variable domain of heavy chain of heavy-chain antibody (VHH) and wildtype IgG1 Fc. Pre-clinical studies have demonstrated that HLX53 exhibits excellent tumour inhibition[11] with good safety. In addition, Henlius has initiated a phase 1 study to evaluate the safety, tolerability, pharmacokinetics and preliminary efficacy of HLX53 in patients with advanced or metastatic solid tumours or lymphomas who have no standard therapy or failed the standard therapy. Considering the good efficacy of immune checkpoint inhibitor such as anti-PD-1/PD-L1 antibody plus anti-angiogenic drug in the first-line treatment of patients with advanced HCC, as well as the synergistic effect of TIGIT and PD-1/PD-L1 signaling pathway, Henlius intends to further combine TIGIT inhibitor based on the standard therapy in order to bring greater clinical benefits to patients with advanced HCC.

Looking forward, Henlius will further accelerate the clinical research of diversified novel portfolio, proactively exploring immuno-oncology combination therapy to provide more effective treatment options to fulfill the unmet clinical needs.


[1] Bray F et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024 Apr 4.

[2] Han B,Zheng R,Zeng H,et al. Cancer incidence and mortality in China,2022[J].Journal of the National Cancer Center, 2024.

[3] 《CSCO原发性肝癌诊疗指南(2022版)》

[4] Asafo-Agyei KO, Samant H. Hepatocellular Carcinoma. 2023 Jun 12. In: StatPearls [Internet].Treasure Island (FL): StatPearls Publishing; 2023 Jan–. PMID: 32644603.

[5] Cheng, Ann-Lii et al. “Updated efficacy and safety data from IMbrave150: Atezolizumab plus bevacizumab vs. sorafenib for unresectable hepatocellular carcinoma.” Journal of hepatology vol. 76,4 (2022): 862-873.

[6] Chauvin JM, Zarour HM. TIGIT in cancer immunotherapy. J Immunother Cancer. 2020;8(2).

[7] Sanchez-Correa B, Valhondo I, Hassouneh F, et al. DNAM-1 and the TIGIT/PVRIG/TACTILE Axis: Novel Immune Checkpoints for Natural Killer Cell-Based Cancer Immunotherapy. Cancers (Basel). 2019;11(6):877.

[8] Yue C, Gao S, Li S, et al. (2022) TIGIT as a Promising Therapeutic Target in Autoimmune Diseases. Front. Immunol. 13:911919.

[9] Zhang, Peng et al. “Targeting TIGIT for cancer immunotherapy: recent advances and future directions.” Biomarker research vol. 12,1 7. 16 Jan. 2024.

[10] Chu, Xianjing et al. “Co-inhibition of TIGIT and PD-1/PD-L1 in Cancer Immunotherapy: Mechanisms and Clinical Trials.” Molecular cancer vol. 22,1 93. 8 Jun. 2023

[11] Hua, B. et al. A novel single domain antibody targeting TIGIT for cancer use in combination therapies. Cancer Research 81, 2451-2451 (2021).